Role of Autoantibodies in Neurodegenerative Dementia: An Emerging Association.

OBJECTIVE: In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer's dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. RESULTS: Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (n = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. CONCLUSION: Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation.

BACKGROUND: Data on antibody profile in myasthenia gravis (MG) from India are limited. OBJECTIVES: To investigate antibody profile in patients with MG and their clinical correlates. PATIENTS AND METHODS: Patients of MG (n = 85, M:F::1.1:1, mean age: 39.29 ± 17.3 years, mean symptom duration: 72.94 ± 91.8 months) were evaluated for clinical features, MG foundation of America (MGFA) score, response to treatment, and outcome at last follow-up. Antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MUSK), titin and ryanodine receptor (RYR) were analysed using ELISA. RESULTS: Based on the regional distribution of weakness, the cohort could be categorized as: generalized: 60, ocular: 16 and oculo-bulbar: 9. Sixty patients were followed up for a mean duration of 26.74 ± 13.8 months. Outcome at last follow-up was as follows: remission-22, no remission-33 and dead-5. AChR and MUSK antibodies were detected in 58 and 8 patients, respectively. Frequency of generalized MG, worse MGFA score during the disease course and thymomatous histology significantly correlated with presence of AChR-antibodies, though outcome at last follow-up was comparable between AChR-antibody positive and negative groups. Patients with MUSK antibodies had oculo-bulbar or generalized MG and frequent respiratory crisis, but majority improved or remitted with treatment. Titin antibodies were detected in 31.8% and RYR antibodies in 32.9%. Their presence did not correlate with age at onset of MG, severity or presence of thymoma. CONCLUSION: This report highlights the spectrum of antibodies in MG in an Indian cohort. AChR-antibody positivity correlated with clinical severity. Outcome was good in majority of MUSK antibody-positive MG. The role of other antibodies, complementary vs epiphenomenon, remains open.

Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease.

BACKGROUND: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. AIMS: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. METHODS: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. RESULTS: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. CONCLUSION: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.