Melike Küçükerden

Switch-Associated Protein 70 Antibodies in Multiple Sclerosis: Possible Association with Disease Progression

Objective: This study was conducted to identify a biomarker for multiple sclerosis (MS) that can be used as a predictor of relapse and disability. Materials and Methods: Sera of 26 consecutive relapsing-remitting MS (RRMS) patients were screened for switch-associated protein 70 (SWAP-70) antibody, which was previously identified by protein macroarray. The serum levels of several cytokines, chemokines and soluble adhesion molecules related to MS attacks were measured by enzyme-linked immunosorbent assay (ELISA). A possible correlation was sought among levels of SWAP-70 antibody, measured humoral factors and disability scores. Results: ELISA studies showed high-titre SWAP-70 antibodies in 16 (61.5%) RRMS sera obtained during the attack period and 9 (34.6%) sera obtained during remission. There was a significant inverse correlation between SWAP-70 antibody levels and expanded disability status scale scores, CXCL10, soluble VCAM-1, CXCL13 and soluble VLA-4 levels. Conclusion: Our results showed that SWAP-70 antibodies could potentially be utilized as relapse and prognostic biomarkers in MS. Whether or not SWAP-70 antibodies have any effect on disease mechanisms requires further investigation.

MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK

Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis.

Sorcin antibody as a possible predictive factor in conversion from radiologically isolated syndrome to multiple sclerosis: a preliminary study.

AbstractObjectiveTo identify an antibody biomarker for prediction of conversion from radiologically isolated syndrome (RIS) to relapsing remitting multiple sclerosis (RRMS).MethodsSera of 13 RIS patients were screened by a protein macroarray derived from human fetal brain cDNA library.ResultsSequencing of a clone with the highest signal intensity revealed sorcin as a potential target autoantigen in RIS patients. ELISA studies showed high-titer sorcin-antibodies in 3 of 4 RIS patients who converted to RRMS in a 5-year follow-up period and 13 of 23 control RRMS patients. Conclusion The value of sorcin antibody as a predictor of conversion from RIS to RRMS requires to be tested in larger prospective studies.

Short term fingolimod treatment decreases soluble VLA 4 levels in MS patients

Multiple sclerosis (MS) is an immune mediated disorder of the central nervous system. T-cells and other immune effector cells play crucial roles in MS pathogenesis by crossing the brain–blood barrier and consequently destroying the myelin sheat and axons. Fingolimod (FTY720) is an oral sphingosine-1-phosphate (S1P) receptor modulator, approved for treatment of MS. Resting T and B lymphocytes express elevated levels of S1P receptor and lymphocyte migration from the lymphoid organs to the brain depends on the activity of this receptor. Recent evidence suggests that fingolimod does not only prevent lymphocyte migration to the central nervous system but also exhibit other mechanisms of action. To investigate the potential effector functions of fingolimod on cytokine, chemokine and soluble adhesion molecule production, levels of IL-17A, IL-10, IL-6, IL-13, IFN-γ, TNFα, IL-4, IL-12p40, soluble VLA4 (sVLA4), sVCAM1, sICAM, CXCL13, CCL2 and IL-8 were measured by ELISA in sera obtained before (S0) and three months after the onset (S3m) of fingolimod treatment in 10 MS patients. Serum sVLA4 levels were significantly decreased in all MS patient’s sera after treatment and sVLA4 levels were significantly lower in S3m sera as compared to S0 sera. By contrast, levels of other examined factors did not show any statistical difference among S0 and S3m sera. These results suggest that in contrast with other immunomodulating agents, shortterm fingolimod treatment does not affect Th1 and Th17 immunities. Reduction of sVLA4 by fingolimod treatment may contribute to prevention of lymphocyte crossing through blood–brain barrier and thus amelioration of MS symptoms.