IgA Nephropathy with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: Expanding the Spectrum of Systemic IgA Disease

IgA Nephropathy with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: Expanding the Spectrum of Systemic IgA Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report IgA Nephropathy with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: Expanding the Spectrum of Systemic IgA Disease Thotanolla Surya Prakash This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7964184/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: IgA nephropathy (IgAN) is the most frequent primary glomerulonephritis worldwide, yet neurological involvement is rarely encountered. Central nervous system (CNS) manifestations such as demyelinating lesions or optic neuritis have been only sporadically described. Recognition of such associations may broaden understanding of systemic immune injury in IgAN. Case Presentation: A 20-year-old man presented with acute, painful visual loss in the right eye, diagnosed as optic neuritis. One week later, he developed edema, oliguria, and malignant hypertension (220/130 mmHg). Investigations revealed elevated serum creatinine (8.4 mg/dL), non-nephrotic proteinuria (2.3 g/day), and normal complement levels. MRI of the cervical spine demonstrated longitudinally extensive transverse myelitis (LETM) spanning C3–C7. Serologic tests for ANA, ANCA, anti-MOG, and anti-AQP4 antibodies were negative. Kidney biopsy showed crescentic IgA nephropathy with mesangial IgA and C3 deposition. The patient was treated with pulse methylprednisolone followed by intravenous cyclophosphamide and supportive hemodialysis, resulting in partial neurological improvement. Discussion: The concurrent occurrence of IgAN, optic neuritis, and LETM suggests a shared immune-mediated vasculitic process. Aberrant galactose-deficient IgA1 may form circulating immune complexes that deposit in both glomerular and CNS microvasculature, triggering localized endothelial injury and demyelination. The absence of hypocomplementemia and systemic features of IgA vasculitis indicates this represents a rare extrarenal expression of IgAN rather than systemic vasculitis. Conclusion: This case highlights that IgA nephropathy can, albeit rarely, present with demyelinating CNS lesions such as LETM and optic neuritis. Awareness of this association facilitates early immunosuppressive therapy, potentially improving neurological and renal outcomes. Urology & Nephrology IgA Nephropathy Crescentic Glomerulonephritis Longitudinally Extensive Transverse Myelitis (LETM) Optic Neuritis Figures Figure 1 Figure 1 Figure 2 Figure 2 Figure 2 Figure 3 Figure 4 Background IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and a major cause of chronic kidney disease. Its hallmark is mesangial deposition of IgA-containing immune complexes. While renal manifestations such as hematuria, proteinuria, and hypertension are common, extrarenal involvement is unusual. However, rare associations with cutaneous vasculitis, arthritis, and gastrointestinal diseases have been described. Neurological complications, particularly central nervous system demyelination, are extremely rare and are only sporadically reported in the literature. Here, we describe a young male with biopsy-proven IgA nephropathy who also developed optic neuritis and longitudinally extensive transverse myelitis (LETM). Case Presentation A 20-year-old male, previously healthy, presented with a two-week history of headache and blurred vision in the right eye. One week later, the patient developed progressive lower-limb swelling and reduced urine output. He was a smoker for one year and an occasional alcohol user, with no history of diabetes, NSAID use, native medicine intake, drug abuse, transfusions, or surgeries. On admission, his blood pressure was 220/130 mmHg. Examination revealed pallor, pedal edema, elevated jugular venous pressure, and decreased vision in the right eye. Fundus examination revealed right optic disc edema and blurring of the disc margins, suggestive of retrobulbar neuritis (Fig. 1 ). Cardiovascular and respiratory examinations were unremarkable. A neurological examination confirmed visual loss without motor or sensory deficits. He underwent further investigations, as mentioned in Table 1. Investigations (Table 1) Test Result Reference/Comment Hemoglobin 8.6 g/dL Low Total leukocyte count 8400 /mm³ Normal Platelet count 1.19 lakh/mm³ Mild thrombocytopenia Serum creatinine 8.4 mg/dL Markedly elevated Urine albumin 4+ Nephrotic range Urine RBCs Plenty Microscopic hematuria 24h urine protein 2.3 g Non Nephrotic range Serum albumin 2.7 g/dL Low C3 85 mg/dL Normal C4 51 mg/dL Normal ANA/ANCA/Anti-GBM Negative Autoimmune screen Anti-MOG, Anti-AQP4 antibodies Negative Excluded Neuro Myelitis OpticabSpectrum Disorder Ultrasound kidneys 9.2–9.3 cm, increased echogenicity, poor Cortico Medullary Differentiation Chronic Kidney Disease changes MRI cervical spine Long segment Longitudinally Extensive Transverse Myelitis (C3–C7, ~ 6.5 cm) Pathological finding CSF analysis Appearance-clear Cell count 40 cells/µl, predominantly lymphocytes Protein-120mg/dl Glucose-50mg/dl No oligoclonal bands Lymphocytic pleocytosis,raised protein,and no oligonal bands s/o immune mediated LETM In view of blurring of vision, he was administered intravenous pulse methylprednisolone (1 g/day intravenously for three days, after which the patient's vision improved. He was initiated on hemodialysis because of oliguria and renal failure. Later, the patient underwent a renal biopsy, which revealed IgA nephropathy with crescents (Figs. 2 a, 2 b). Figure 2 a: Hematoxylin and eosin (H&E) staining of renal biopsy revealing a crescent (black arrow). The rest of the glomeruli showed mesangial proliferation, the basement membrane appeared normal, and no segmental sclerosis or globalglomerulosclerosis was seen in 5 out of 8 glomeruli, with interstitial fibrosis and tubular atrophy of 35%. arterioles were unremarkable. Immunofluorescence revealed mesangial IgA-3 + and C32 + deposition, while the rest were negative. He was administered intravenous cyclophosphamide (1 g) in view of the crescents in the biopsy. He underwent ninesessions of hemodialysis. His urine output did not improve and his serum creatinine level was 9 mg/dl. As part of the evaluation for retrobulbar neuritis, the patient underwent magnetic resonance imaging (MRI) of the brain and cervical spine, which revealed longitudinally extensive transverse myelitis (Fig. 3 ). Anti-aquaporin-4 and anti-myelin oligodendrocyte (myelin oligodendrocyte) antibodies were negative. CSF analysis revealed lymphocytic pleocytosis with a mild increase in protein content and normal glucose levels, suggesting anautoimmune etiology. Discussion IgA nephropathy (IgAN) is the most common cause of chronic kidney disease of glomerular origin and usually presents as progressive renal failure, proteinuria, or recurrent hematuria [1]. Although rare, extrarenal IgAN manifestations can affect the gastrointestinal tract, joints, and skin [2]. However, neurological involvement is extremely uncommon; only a few case studies have linked IgAN to central nervous system demyelination [3]. Our patient presented with two distinct neurological features: optic neuritis and longitudinally extensive transverse myelitis (LETM). LETM, defined as a spinal cord lesion extending over three or more vertebral segments, is classically associated with neuromyelitis optica spectrum disorder (NMOSD) [4]. However, in the present case, both anti-aquaporin-4 and anti-MOG antibodies were negative, ruling out NMOSD. The coexistence of LETM and IgAN suggests a possible immune-mediated link. IgA vasculitis has been associated with CNS involvement in the literature rather than IgA nephropathy.The accumulation of IgA-containing complexes in the venules, capillaries, and arterioles is a hallmark of IgAV, a systemic vasculitis.Rarely does IgAV involve the central nervous system; it mostly affects patients with arterial hypertension, renal dysfunction, and multiorgan disease.the mechanism by which CNS is involved in IgA vasculitis the mechanisms of cns involvement in igA vasculitis are: Aberrant IgA1 production.In IgAN, there is an overproduction of a structurally abnormal subtype of immunoglobulin A1 (IgA1) with a galactose-deficient hinge region (Gd-IgA1). This altered glycosylation pattern causes the molecule to be recognized as antigenic by the host immune system, thereby promoting autoantibody formation ( 5 , 6 ). These galactose-deficient IgA1 molecules bind to circulating IgG or IgA autoantibodies, forming large immune complexes that are inefficiently cleared by the liver and persist in circulation ( 5 , 7 ). While these immune complexes are typically deposited in the glomeruli, they can also affect other small vessels throughout the body. In rare cases, deposition within the spinal cord microvasculature can occur, similar to the vascular pathology observed in IgA vasculitis (Henoch–Schönlein purpura), suggesting a shared pathogenic spectrum between IgAN and systemic IgA vasculitis ( 8 ). Deposition of immune complexes activates the complement system and triggers leukocytoclastic vasculitis, damaging endothelial cells and leading to microthrombus formation and vascular occlusion. This impairs spinal cord perfusion, resulting in localized ischemia and hypoxia ( 9 ). Ischemic insult induces inflammation and demyelination of the spinal cord. The resulting lesion, which may extend over multiple vertebral segments, is characteristic of LETM. The associated nerve fiber injury disrupts signal conductionand causes sensory and motor deficits ( 10 ). LETM has never been previously reported to be associated with IgA vasculitis. Our patient had igA nephropathy, which was proven by renal biopsy,who also had LETM. This raised the question of whether its association of IgA nephropathy or IgA vasculitis.IgA vasculitis (IgAV) has been more commonly associated with central nervous system involvement than IgA nephropathy (IgAN). The pathogenesis of IgAV involves deposition of IgA-containing immune complexes in small vessels and subsequent complement activation, particularly through the alternative and lectin pathways, often leading to reduced serum complement levels. Our patient, however, had normal complement (C3 and C4) values and lacked other systemic vasculitic features, there by making IgAV unlikely. These findings suggest that the coexistence of IgAN with LETM in this case represents a rare manifestation of IgAN itself rather than IgAV. The normal complement profile indicates the absence of systemic complement consumption was absent, raising the possibility of localized immune-complex deposition or endothelial dysfunction within the CNS microvasculature. CSF analysis showed mild lymphocytic pleocytosis and elevated protein without oligoclonal bands, findings compatible with a localized immune-mediated inflammatory process confined to the CNS.This supports a model in which galactose-deficient IgA1 immune complexes, central to the IgAN “four-hit” hypothesis, may trigger localized vascular inflammation through molecular mimicry or focal immune activation, even in the absence of systemic complement abnormalities.( 11 ) Although extremely uncommon, longitudinally extensive transverse myelitis (LETM) associated with IgA nephropathy (IgAN) is thought to result from systemic immune-mediated vasculitis. The same circulating immune complexes that cause glomerular injury in IgAN may also affect small-caliber vessels of the spinal cord, leading to inflammation, ischemia, and neural damage. In summary, IgAN-associated LETM likely reflects a rare systemic manifestation of IgA immune complex deposition in which spinal microvascular injury parallels renal glomerular damage. Optic neuritis is uncommon in patients with IgAN. Although optic neuritis is most frequently associated with NMOSD or multiple sclerosis, its occurrence in IgAN suggests that systemic immune dysregulation may be involved [12]. Inflammatory demyelination may result from abnormal mucosal immunity and IgA immune complex deposition in the renal glomeruli, as well as in the CNS microvasculature [13]. Concurrent renal and neurological manifestations highlight the importance of considering IgAN in the differential diagnosis of patients with unexplained acute kidney injury and demyelinating neurological syndromes. Early recognition and a multidisciplinary approach are crucial because both renal and neurological outcomes depend on prompt intervention. Declarations Ethics approval- not applicable as it is a case report Consent to participate and publication: Written and informed consent was obtained from the corresponding author. Availability of data and materials: not applicable Authors contribution: surya and namesh :- manuscript writing Jeeja ,vishwa teja and srikanth :collected images and manuscript writing Competing intersts : none Acknowledgements: none Funding :none Written and informed consent for publication was obtained from the patient. References Wyatt RJ, Julian BA (2013) IgA nephropathy. N Engl J Med 368(25):2402–2414 Lai KN, Tang SC, Schena FP, Novak J, Tomino Y, Fogo AB et al (2016) IgA nephropathy. Nat Rev Dis Primers 2:16001 Shi Y, Chen X, Ma J, Zhou Y, Li H, Li P et al (2019) Central nervous system involvement in IgA nephropathy: a case report and literature review. BMC Nephrol 20(1):256 Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189 Xu W, He X, He J et al (2022) IgA Vasculitis Update: Epidemiology, Pathogenesis, and Biomarker. Front Immunol 13:921864 Suzuki H, Novak J (2023) IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings. J Clin Med 13(15):4495 Song Y, Huang X, Xu W (2021) Pathogenesis of IgA Vasculitis: An Up-To-Date Review. Front Immunol 12:771619 Pillebout E, Sunderkötter C (2021) IgA Vasculitis and IgA Nephropathy: Same Disease? J Clin Med 10(11):2310 Guo L, Li Y, Wang C et al (2024) IgA Vasculitis with Central Nervous System Involvement: A Case Report and Literature Review. Front Neurol 15:12064608 Guo Z, Li S, Liu C, Zhu Z, Wang P, Yang Y, Du L (2025) Immunoglobulin A vasculitis with central nervous system involvement: analysis of 10 cases. Clin Exp Med 25:145. 10.1007/s10238-025-01679-y Colantonio S, Rossi D, Toma M et al (2024) An Unusual Presentation of IgA Vasculitis with Neurological Manifestations. Case Rep Med. ; Article ID 12315905. Toosy AT, Mason DF, Miller DH (2014) Optic neuritis. Lancet Neurol 13(1):83–99 Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Maier M, Zhang X et al (2011) The pathophysiology of IgA nephropathy. J Am Soc Nephrol 22(10):1795–1806 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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The fundus picture of the left eye shows grade 2 hypertensive retinopathy changes.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/e1cc83ae310508a91883303a.png"},{"id":94966066,"identity":"8ea0b429-9005-429e-beb1-9eac89d92b1b","added_by":"auto","created_at":"2025-11-02 20:43:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":271954,"visible":true,"origin":"","legend":"\u003cp\u003eFundus image of the right eye showing blurring of the disc margin, elevated disc, and few peripapillary hemorrhages (suggestive of optic neuritis) in a background of grade 2 hypertensive retinopathy. The fundus picture of the left eye shows grade 2 hypertensive retinopathy changes.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/8e6ab8f6bb5ceffcd03a2837.png"},{"id":94988427,"identity":"16939008-e14d-4df0-9210-41b442c98230","added_by":"auto","created_at":"2025-11-03 07:08:59","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":308035,"visible":true,"origin":"","legend":"\u003cp\u003ea: Hematoxylin and eosin (H\u0026amp;E) staining of renal biopsy revealing a crescent (black arrow). The rest of the glomeruli showed mesangial proliferation, the basement membrane appeared normal, and no segmental sclerosis or globalglomerulosclerosis was seen in 5 out of 8 glomeruli, with interstitial fibrosis and tubular atrophy of 35%. arterioles were unremarkable.\u003c/p\u003e\n\u003cp\u003eb:PAS staining of renal biopsy revealing mesangial proliferation (black arrows) with collapse of arterioles.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Image2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/1bc6594cd9c77ad027dc14c1.jpg"},{"id":94988236,"identity":"5ee7921e-eb4a-40ce-9a57-ebb757bb55c2","added_by":"auto","created_at":"2025-11-03 07:07:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":885136,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2a: Hematoxylin and eosin (H\u0026amp;E) staining of renal biopsy revealing a crescent (black arrow). The rest of the glomeruli showed mesangial proliferation, the basement membrane appeared normal, and no segmental sclerosis or globalglomerulosclerosis was seen in 5 out of 8 glomeruli, with interstitial fibrosis and tubular atrophy of 35%. arterioles were unremarkable.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/3b20cdb47553d7026358d0ae.png"},{"id":94966085,"identity":"0720e615-b1b1-4dfe-b6c7-147a5e583616","added_by":"auto","created_at":"2025-11-02 20:44:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":308035,"visible":true,"origin":"","legend":"\u003cp\u003ea: Hematoxylin and eosin (H\u0026amp;E) staining of renal biopsy revealing a crescent (black arrow). The rest of the glomeruli showed mesangial proliferation, the basement membrane appeared normal, and no segmental sclerosis or globalglomerulosclerosis was seen in 5 out of 8 glomeruli, with interstitial fibrosis and tubular atrophy of 35%. arterioles were unremarkable.\u003c/p\u003e\n\u003cp\u003eb:PAS staining of renal biopsy revealing mesangial proliferation (black arrows) with collapse of arterioles.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Image2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/43e6551557297ddabe39a73a.jpg"},{"id":94966067,"identity":"e4ca90f9-e1b8-4331-905c-02a78e8d53f1","added_by":"auto","created_at":"2025-11-02 20:43:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":706470,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Cervical spine revealing longitudinally extensive transverse myelitis (LETM) extending from C3 to C7 segments. A workup of the LETM was performed.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Picture3.png","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/a8b2a8fa332402c530411c72.png"},{"id":94988825,"identity":"e5de8a53-666c-4426-98d5-e74f1c81782a","added_by":"auto","created_at":"2025-11-03 07:11:05","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":706470,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3:MRI Cervical spine revealing longitudinally extensive transverse myelitis (LETM) extending from C3 to C7 segments. A workup of the LETM was performed.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/3e92d57d82f5b55925d18586.png"},{"id":95523451,"identity":"2eb580e3-ace0-4933-b1db-3d23ac9d2078","added_by":"auto","created_at":"2025-11-10 09:55:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5258149,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7964184/v1/749cd982-563b-4117-8289-1d26bc6a1704.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eIgA Nephropathy with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: Expanding the Spectrum of Systemic IgA Disease\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eIgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and a major cause of chronic kidney disease. Its hallmark is mesangial deposition of IgA-containing immune complexes. While renal manifestations such as hematuria, proteinuria, and hypertension are common, extrarenal involvement is unusual. However, rare associations with cutaneous vasculitis, arthritis, and gastrointestinal diseases have been described. Neurological complications, particularly central nervous system demyelination, are extremely rare and are only sporadically reported in the literature. Here, we describe a young male with biopsy-proven IgA nephropathy who also developed optic neuritis and longitudinally extensive transverse myelitis (LETM).\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 20-year-old male, previously healthy, presented with a two-week history of headache and blurred vision in the right eye. One week later, the patient developed progressive lower-limb swelling and reduced urine output. He was a smoker for one year and an occasional alcohol user, with no history of diabetes, NSAID use, native medicine intake, drug abuse, transfusions, or surgeries.\u003c/p\u003e\u003cp\u003eOn admission, his blood pressure was 220/130 mmHg. Examination revealed pallor, pedal edema, elevated jugular venous pressure, and decreased vision in the right eye. Fundus examination revealed right optic disc edema and blurring of the disc margins, suggestive of retrobulbar neuritis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Cardiovascular and respiratory examinations were unremarkable. A neurological examination confirmed visual loss without motor or sensory deficits. He underwent further investigations, as mentioned in Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eInvestigations (Table\u0026nbsp;1)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTest\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResult\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference/Comment\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.6 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal leukocyte count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8400 /mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.19 lakh/mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMild thrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum creatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.4 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMarkedly elevated\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrine albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNephrotic range\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrine RBCs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePlenty\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMicroscopic hematuria\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.3 g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon Nephrotic range\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.7 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eANA/ANCA/Anti-GBM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAutoimmune screen\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-MOG, Anti-AQP4 antibodies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExcluded Neuro Myelitis OpticabSpectrum Disorder\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound kidneys\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.2\u0026ndash;9.3 cm, increased echogenicity, poor Cortico Medullary Differentiation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChronic Kidney Disease changes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMRI cervical spine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLong segment Longitudinally Extensive Transverse Myelitis (C3\u0026ndash;C7, ~\u0026thinsp;6.5 cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePathological finding\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAppearance-clear\u003c/p\u003e\u003cp\u003eCell count 40 cells/\u0026micro;l,\u003c/p\u003e\u003cp\u003epredominantly lymphocytes\u003c/p\u003e\u003cp\u003eProtein-120mg/dl\u003c/p\u003e\u003cp\u003eGlucose-50mg/dl\u003c/p\u003e\u003cp\u003eNo oligoclonal bands\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLymphocytic pleocytosis,raised protein,and no oligonal bands s/o immune mediated LETM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn view of blurring of vision, he was administered intravenous pulse methylprednisolone (1 g/day intravenously for three days, after which the patient's vision improved. He was initiated on hemodialysis because of oliguria and renal failure. Later, the patient underwent a renal biopsy, which revealed IgA nephropathy with crescents (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea: Hematoxylin and eosin (H\u0026amp;E) staining of renal biopsy revealing a crescent (black arrow). The rest of the glomeruli showed mesangial proliferation, the basement membrane appeared normal, and no segmental sclerosis or globalglomerulosclerosis was seen in 5 out of 8 glomeruli, with interstitial fibrosis and tubular atrophy of 35%. arterioles were unremarkable.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eImmunofluorescence revealed mesangial IgA-3\u0026thinsp;+\u0026thinsp;and C32\u0026thinsp;+\u0026thinsp;deposition, while the rest were negative.\u003c/p\u003e\u003cp\u003eHe was administered intravenous cyclophosphamide (1 g) in view of the crescents in the biopsy. He underwent ninesessions of hemodialysis. His urine output did not improve and his serum creatinine level was 9 mg/dl. As part of the evaluation for retrobulbar neuritis, the patient underwent magnetic resonance imaging (MRI) of the brain and cervical spine, which revealed longitudinally extensive transverse myelitis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAnti-aquaporin-4 and anti-myelin oligodendrocyte (myelin oligodendrocyte) antibodies were negative. CSF analysis revealed lymphocytic pleocytosis with a mild increase in protein content and normal glucose levels, suggesting anautoimmune etiology.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIgA nephropathy (IgAN) is the most common cause of chronic kidney disease of glomerular origin and usually presents as progressive renal failure, proteinuria, or recurrent hematuria [1]. Although rare, extrarenal IgAN manifestations can affect the gastrointestinal tract, joints, and skin [2]. However, neurological involvement is extremely uncommon; only a few case studies have linked IgAN to central nervous system demyelination [3].\u003c/p\u003e\u003cp\u003eOur patient presented with two distinct neurological features: optic neuritis and longitudinally extensive transverse myelitis (LETM). LETM, defined as a spinal cord lesion extending over three or more vertebral segments, is classically associated with neuromyelitis optica spectrum disorder (NMOSD) [4]. However, in the present case, both anti-aquaporin-4 and anti-MOG antibodies were negative, ruling out NMOSD. The coexistence of LETM and IgAN suggests a possible immune-mediated link.\u003c/p\u003e\u003cp\u003eIgA vasculitis has been associated with CNS involvement in the literature rather than IgA nephropathy.The accumulation of IgA-containing complexes in the venules, capillaries, and arterioles is a hallmark of IgAV, a systemic vasculitis.Rarely does IgAV involve the central nervous system; it mostly affects patients with arterial hypertension, renal dysfunction, and multiorgan disease.the mechanism by which CNS is involved in IgA vasculitis the mechanisms of cns involvement in igA vasculitis are:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAberrant IgA1 production.In IgAN, there is an overproduction of a structurally abnormal subtype of immunoglobulin A1 (IgA1) with a galactose-deficient hinge region (Gd-IgA1). This altered glycosylation pattern causes the molecule to be recognized as antigenic by the host immune system, thereby promoting autoantibody formation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThese galactose-deficient IgA1 molecules bind to circulating IgG or IgA autoantibodies, forming large immune complexes that are inefficiently cleared by the liver and persist in circulation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eWhile these immune complexes are typically deposited in the glomeruli, they can also affect other small vessels throughout the body. In rare cases, deposition within the spinal cord microvasculature can occur, similar to the vascular pathology observed in IgA vasculitis (Henoch\u0026ndash;Sch\u0026ouml;nlein purpura), suggesting a shared pathogenic spectrum between IgAN and systemic IgA vasculitis (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eDeposition of immune complexes activates the complement system and triggers leukocytoclastic vasculitis, damaging endothelial cells and leading to microthrombus formation and vascular occlusion. This impairs spinal cord perfusion, resulting in localized ischemia and hypoxia (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIschemic insult induces inflammation and demyelination of the spinal cord. The resulting lesion, which may extend over multiple vertebral segments, is characteristic of LETM. The associated nerve fiber injury disrupts signal conductionand causes sensory and motor deficits (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eLETM has never been previously reported to be associated with IgA vasculitis.\u003c/p\u003e\u003cp\u003eOur patient had igA nephropathy, which was proven by renal biopsy,who also had LETM. This raised the question of whether its association of IgA nephropathy or IgA vasculitis.IgA vasculitis (IgAV) has been more commonly associated with central nervous system involvement than IgA nephropathy (IgAN). The pathogenesis of IgAV involves deposition of IgA-containing immune complexes in small vessels and subsequent complement activation, particularly through the alternative and lectin pathways, often leading to reduced serum complement levels. Our patient, however, had normal complement (C3 and C4) values and lacked other systemic vasculitic features, there by making IgAV unlikely. These findings suggest that the coexistence of IgAN with LETM in this case represents a rare manifestation of IgAN itself rather than IgAV. The normal complement profile indicates the absence of systemic complement consumption was absent, raising the possibility of localized immune-complex deposition or endothelial dysfunction within the CNS microvasculature. CSF analysis showed mild lymphocytic pleocytosis and elevated protein without oligoclonal bands, findings compatible with a localized immune-mediated inflammatory process confined to the CNS.This supports a model in which galactose-deficient IgA1 immune complexes, central to the IgAN \u0026ldquo;four-hit\u0026rdquo; hypothesis, may trigger localized vascular inflammation through molecular mimicry or focal immune activation, even in the absence of systemic complement abnormalities.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eAlthough extremely uncommon, longitudinally extensive transverse myelitis (LETM) associated with IgA nephropathy (IgAN) is thought to result from systemic immune-mediated vasculitis. The same circulating immune complexes that cause glomerular injury in IgAN may also affect small-caliber vessels of the spinal cord, leading to inflammation, ischemia, and neural damage.\u003c/p\u003e\u003cp\u003eIn summary, IgAN-associated LETM likely reflects a rare systemic manifestation of IgA immune complex deposition in which spinal microvascular injury parallels renal glomerular damage.\u003c/p\u003e\u003cp\u003eOptic neuritis is uncommon in patients with IgAN. Although optic neuritis is most frequently associated with NMOSD or multiple sclerosis, its occurrence in IgAN suggests that systemic immune dysregulation may be involved [12]. Inflammatory demyelination may result from abnormal mucosal immunity and IgA immune complex deposition in the renal glomeruli, as well as in the CNS microvasculature [13].\u003c/p\u003e\u003cp\u003eConcurrent renal and neurological manifestations highlight the importance of considering IgAN in the differential diagnosis of patients with unexplained acute kidney injury and demyelinating neurological syndromes. Early recognition and a multidisciplinary approach are crucial because both renal and neurological outcomes depend on prompt intervention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval- not applicable as it is a case report\u003c/p\u003e\n\u003cp\u003eConsent\u0026nbsp;to participate and publication:\u0026nbsp;Written\u0026nbsp;and informed consent\u0026nbsp;was obtained\u0026nbsp;from the\u0026nbsp;corresponding author.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: not applicable\u003c/p\u003e\n\u003cp\u003eAuthors contribution: surya and namesh :- manuscript writing\u003c/p\u003e\n\u003cp\u003eJeeja ,vishwa teja and srikanth :collected images and manuscript writing\u003c/p\u003e\n\u003cp\u003eCompeting intersts : none\u003c/p\u003e\n\u003cp\u003eAcknowledgements: none\u003c/p\u003e\n\u003cp\u003eFunding :none\u003c/p\u003e\u003cp\u003eWritten and informed consent for publication was obtained from the patient.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWyatt RJ, Julian BA (2013) IgA nephropathy. N Engl J Med 368(25):2402\u0026ndash;2414\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLai KN, Tang SC, Schena FP, Novak J, Tomino Y, Fogo AB et al (2016) IgA nephropathy. Nat Rev Dis Primers 2:16001\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShi Y, Chen X, Ma J, Zhou Y, Li H, Li P et al (2019) Central nervous system involvement in IgA nephropathy: a case report and literature review. BMC Nephrol 20(1):256\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177\u0026ndash;189\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu W, He X, He J et al (2022) IgA Vasculitis Update: Epidemiology, Pathogenesis, and Biomarker. Front Immunol 13:921864\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuzuki H, Novak J (2023) IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings. J Clin Med 13(15):4495\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong Y, Huang X, Xu W (2021) Pathogenesis of IgA Vasculitis: An Up-To-Date Review. Front Immunol 12:771619\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePillebout E, Sunderk\u0026ouml;tter C (2021) IgA Vasculitis and IgA Nephropathy: Same Disease? J Clin Med 10(11):2310\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo L, Li Y, Wang C et al (2024) IgA Vasculitis with Central Nervous System Involvement: A Case Report and Literature Review. Front Neurol 15:12064608\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo Z, Li S, Liu C, Zhu Z, Wang P, Yang Y, Du L (2025) Immunoglobulin A vasculitis with central nervous system involvement: analysis of 10 cases. Clin Exp Med 25:145. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10238-025-01679-y\u003c/span\u003e\u003cspan address=\"10.1007/s10238-025-01679-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eColantonio S, Rossi D, Toma M et al (2024) An Unusual Presentation of IgA Vasculitis with Neurological Manifestations. Case Rep Med. ; Article ID 12315905.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eToosy AT, Mason DF, Miller DH (2014) Optic neuritis. Lancet Neurol 13(1):83\u0026ndash;99\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuzuki H, Kiryluk K, Novak J, Moldoveanu Z, Maier M, Zhang X et al (2011) The pathophysiology of IgA nephropathy. J Am Soc Nephrol 22(10):1795\u0026ndash;1806\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Sri Venkateswara Institute of Medical Sciences","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"IgA Nephropathy, Crescentic Glomerulonephritis, Longitudinally Extensive Transverse Myelitis (LETM), Optic Neuritis","lastPublishedDoi":"10.21203/rs.3.rs-7964184/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7964184/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003cbr\u003e\nIgA nephropathy (IgAN) is the most frequent primary glomerulonephritis worldwide, yet neurological involvement is rarely encountered. Central nervous system (CNS) manifestations such as demyelinating lesions or optic neuritis have been only sporadically described. Recognition of such associations may broaden understanding of systemic immune injury in IgAN.\u003c/p\u003e\n\u003cp\u003eCase Presentation:\u003cbr\u003e\nA 20-year-old man presented with acute, painful visual loss in the right eye, diagnosed as optic neuritis. One week later, he developed edema, oliguria, and malignant hypertension (220/130 mmHg). Investigations revealed elevated serum creatinine (8.4 mg/dL), non-nephrotic proteinuria (2.3 g/day), and normal complement levels. MRI of the cervical spine demonstrated longitudinally extensive transverse myelitis (LETM) spanning C3–C7. Serologic tests for ANA, ANCA, anti-MOG, and anti-AQP4 antibodies were negative. Kidney biopsy showed crescentic IgA nephropathy with mesangial IgA and C3 deposition. The patient was treated with pulse methylprednisolone followed by intravenous cyclophosphamide and supportive hemodialysis, resulting in partial neurological improvement.\u003c/p\u003e\n\u003cp\u003eDiscussion:\u003cbr\u003e\nThe concurrent occurrence of IgAN, optic neuritis, and LETM suggests a shared immune-mediated vasculitic process. Aberrant galactose-deficient IgA1 may form circulating immune complexes that deposit in both glomerular and CNS microvasculature, triggering localized endothelial injury and demyelination. The absence of hypocomplementemia and systemic features of IgA vasculitis indicates this represents a rare extrarenal expression of IgAN rather than systemic vasculitis.\u003c/p\u003e\n\u003cp\u003eConclusion:\u003cbr\u003e\nThis case highlights that IgA nephropathy can, albeit rarely, present with demyelinating CNS lesions such as LETM and optic neuritis. Awareness of this association facilitates early immunosuppressive therapy, potentially improving neurological and renal outcomes.\u003c/p\u003e","manuscriptTitle":"IgA Nephropathy with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: Expanding the Spectrum of Systemic IgA Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-02 09:24:27","doi":"10.21203/rs.3.rs-7964184/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"25079c25-90d6-4a6a-a49c-19927182f9a3","owner":[],"postedDate":"November 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56981993,"name":"Urology \u0026 Nephrology"}],"tags":[],"updatedAt":"2025-11-02T09:24:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-02 09:24:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7964184","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7964184","identity":"rs-7964184","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}