Relapsing Evans syndrome and systemic lupus erythematosus with antiphospholipid syndrome treated with Bortezomib in combination with plasma exchange.

Relapsing Evans syndrome (ES) and systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) is very rare association. Coexistence of these syndromes is potentially fatal and require high-dose combined immunosuppressive therapy. We describe a case of successful use of Bortezomib and plasma exchange in a patient with ES and APS refractory to standard therapy. Thirty-two-year-old male who presented episodes of relapsing hemolytic anemia, pancytopenia and multiple thrombosis with positive direct and indirect antiglobulin test result, lupus anticoagulant and medium titer of anti-beta-2-glycoprotein 1 and anti-cardiolipin antibodies was diagnosed with ES and SLE with secondary APS. High-dose therapy by steroids and Cyclosporin A were started with temporary improvement. There was also no stable improvement with Rituximab and Cyclophosphamide. Bortezomib in combination with cyclosporine A and plasma exchange was introduced. He had stable improvement in hematological parameters with no evidence of relapse of hemolytic crisis or thrombosis during a follow-up for 1 year.

Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis.

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included. Kappa and lambda FLC concentrations in serum and cerebrospinal fluid (CSF) samples of MS patients were measured using ELISA assay. FLC quotients (Q-k and Q-λ, respectively) were calculated. In a cross-sectional group (n = 92), the MRI data were acquired within 6 months from the date of the lumbar puncture. Twenty patients from this cohort performed a follow-up MRI after 1 year of observation. Brain volumes were calculated with SIENAX and the brain atrophy (percentage brain volume change (PBVC)) was assessed with SIENA. Spearman's test was performed to assess correlations. We have shown statistically significant correlation of Expanded Disability Status Scale (EDSS) level with normalized brain volume (NBV, r = - 0.2721, p = 0.0062), white matter volume (WMV, r = - 0.2425, p = 0.015), and gray matter volume (GMV, r = - 0.216, p = 0.0309). Multiple Sclerosis Severity Score (MSSS) score correlated with NBV (r = - 0.2521, p = 0.0352) and WMV (r = - 0.315, p = 0.0079). Neither EDSS, nor MSSS scores correlated with the age of patients and relapse rate during the first year and 5 years. In our study, we found statistically significant correlations of k-FLC in the CSF with NBV (r = - 0.311, p = 0.003) and with GMV (r = - 0.213, p = 0.0423). Q-k correlated only with NBV (r = - 0.340, p = 0.006) and Q-λ were negatively correlated with WMV (r = - 0.366, p = 0.003). We did not find correlations of k-FLC in CSF, λ-FLC in CSF, Q-k, and Q-λ with duration of MS course, EDSS, MSSS, number of relapses during the first year, and during the first 5 years of disease. Additionally, we subdivided the study population in accordance with level of k-FLC CSF, Q-k, and Q-λ on the 25th and 75th percentile subgroups (25-k-FLCCSF/75-k-FLCCSF; 25-λ-FLCCSF/75-λ-FLCCSF; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLCCSF and 75-k-FLCCSF subgroups (p = 0.0047, p = 0.0297 respectively), NBV between 25-Q-k and 75-Q-k subgroups (p = 0.038), and NBV and WMV between 25-Q-λ and 75-Q-λ subgroups (p = 0.0446, p = 0.0026 respectively). PBVC in the prospective group showed negative correlation with kappa FLC in the CSF (r = - 0.4853, p = 0.0301) and Q-k (r = - 0.6132, p = 0.0224), but not with other clinical, epidemiological data. In this study, we showed a strong negative correlation of k-FLC, Q-k, and Q-λ with brain atrophy in MS patients. Additionally, patients with high concentration of FLC had lower brain volumes. We did not find correlations of FLC with the relapse rate, age of patients, and MS time course. In the prospective group, the rate of atrophy was correlated with k-FLC and Q-k. We suggest that level of intrathecal production of FLC can be a good prognostic biomarker for MS.

Vitamin D, Cathelicidin, Prolactin, Autoantibodies, and Cytokines in Different Forms of Pulmonary Tuberculosis versus Sarcoidosis.

BACKGROUND: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. OBJECTIVES: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis. METHODS: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis. RESULTS: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. CONCLUSIONS: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation.