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Immunoglobulins free light chains (FLCs) are assayable in several biological fluids. Currently, there are no reports on FLCs in seminal plasma. The aims of our study were to investigate the presence and detectability of FLCs in seminal plasma and to evaluate the usefulness of this assay in the diagnostic approach to infertile patients. We enrolled 61 patients aged 18-- 50 years. Semen analysis was performed. They were divided into four groups: controls-- normozoospermic, 10 patients, mean ± SEM age 35 ± 1.5 years; varicoceles (VAR), 18 patients aged 24.3 ± 0.96 years; inflammatory (INF) seminal fluids, 24 patients, aged 38.8 ± 2.2 years; and varicoceles and inflammatory (VAR/INF) seminal fluids, 9 patients, aged 29.5 ± 0.71 years. A trend towards higher λ FLCs levels was evidenced in the INF and VAR/INF groups. FLCs were higher in normozoospermic patients with lower levels in VAR, both isolated and associated with inflammatory parameters. This differential pattern of the two types of FLCs reached statistical significance when comparing /λ ratio, with significant lower levels in VAR vs controls. This is the first report of FLCs assay in seminal plasma. We can hypothesize that λ FLCs are increased in inflammatory processes, whether FLCs seem to be influenced by other molecular mechanisms related to varicocele. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small-vessel vasculitis that may evolve into an overt B-cell non-Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV- and 2 HBV-related), treated with low-dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme-linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post-treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of "dormant" B cell clones' activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome. [ABSTRACT FROM AUTHOR]

In the natural history of SARS‐CoV‐2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre‐existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID‐19 are still unclear but the liver damage in SARS‐CoV‐2 infection seems to be directly caused by virus‐induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS‐CoV‐2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID‐19 in patients with pre‐existing liver diseases. [ABSTRACT FROM AUTHOR]

Objective: Genetic factors predisposing to late‐onset myasthenia gravis (LOMG) have not been clearly defined yet. However, genome‐wide association studies identified Human Leukocyte Antigen (HLA) Class II alleles as a hotspot in this disease subtype. The aim of this study was to analyze the correlations of HLA Class II alleles with clinical data and titin antibodies in this patient subgroup. Methods: This study consecutively enrolled anti‐acetylcholine receptor antibody‐positive, non‐thymoma patients with generalized LOMG. All patients were of Italian ancestry. HLA‐DRB1 and ‐DQB1 genotyping and serum titin antibody testing were performed in this population. Results: A total of 107 patients (females: 28/107, 26.2%; median age of onset: 68 years, range: 50‐92) were included. We found a positive association with HLA‐DRB1*07 (P = 1.1 × 10‐5), HLA‐DRB1*14 (P = 0.0251) and HLA‐DQB1*02 (P = 0.0095). HLA‐DRB1*03, HLA‐DRB1*11, and HLA‐DQB1*03 were protective alleles (P = 7.9 × 10‐5, P = 0.0104, and P = 0.0067, respectively). By conditional haplotype analysis, HLA‐DRB1*07‐DQB1*02 was found to be the major risk haplotype (OR = 4.10; 95% C.I.: 2.80‐5.99; P = 6.01 × 10‐11). The mean age at onset was 73.4 years in DRB1*07 homozygotes, 69.7 years in heterozygotes, and 66.6 in non‐carriers (P = 0.0488). DRB1*07 carriers and non‐carriers did not differ in disease severity and response to therapy. Titin antibodies were detected in 61.4% of the cases, having no association with HLA alleles or specific clinical characteristics. Interpretation: In our study, we identified the HLA DRB1*07‐DQB1*02 haplotype as a predisposing factor for the development of generalized LOMG in the Italian population. [ABSTRACT FROM AUTHOR]

Clinical spectrum of hepatitis C virus (HCV)‐related cryoglobulinemia varies from an asymptomatic presentation to severe vasculitis and lymphoma. A recent study in HCV‐negative patients suggests that low cryoglobulins (CGs) levels are responsible for severe renal and neurological complications. The aim of this study was to identify a panel of serological biomarkers associated with low levels of CGs in HCV‐positive patients. We studied a population of 79 untreated patients with chronic HCV infection: 13 naïve patients without CGs; 28 patients with asymptomatic mixed cryoglobulinemia (MC) and low levels of CGs (16/28 with polyclonal type III and 12/28 with microheterogeneous type III CGs); 38 patients with symptomatic MC and high levels of type II CGs. Serum samples were collected and examined for rheumatoid factor (RF) IgG and IgM, free light chains (FLCs) and C3 and C4 complement components. We found that RF‐IgG and IgM, free k chains and k+λ were increased while C4 component was reduced, both in symptomatic and asymptomatic patients. Our results suggest that, even in absence of MC symptoms, the low levels of CGs may represent a trigger of activation for immune system in course of HCV infection. The identification of a correlated biomarkers panel could improve the clinical management of these patients and pave the way for target treatment strategies. © 2018 BioFactors, 45(3):318–325, 2019 [ABSTRACT FROM AUTHOR]

Abstract: In recent years, rituximab (RTX), a monoclonal antibody that binds the B lymphocyte membrane protein CD20, has been increasingly used for the treatment of autoimmune diseases, with the rationale of destroying pathogenic B lymphocytes and decreasing autoantibody formation. Surprisingly, RTX has also proven effective in predominantly T cell–mediated diseases, raising the question whether additional mechanisms may play roles in determining the therapeutic response. Here, we review the current literature on the effects of RTX in autoimmune diseases, with special emphasis on myasthenia gravis (MG). To elicit a complete and effective immune response, B and T lymphocytes cooperate in a loop in which they affect each other. Disruption of this cross talk has profound effects on the immune system. RTX is likely to affect the whole spectrum of B cell function, including antigen presentation, cytokine production, and T cell stimulation. In addition, as a small subset of T lymphocytes expresses CD20, its direct targeting by RTX may contribute to the therapeutic effect. Owing to its distinctive immune characteristics, MG proved to be a useful model to investigate the multifaceted implications of B cell depletion. [ABSTRACT FROM AUTHOR]

Abstract: Myasthenia gravis with antibodies to the muscle‐specific tyrosine kinase (MuSK+ MG) is a rare disease with distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very common and highly suggestive of the disease. On the other hand, a more indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. Though MuSK+ MG is still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment. Despite the improved management, MuSK+ MG patients tend to remain dependent on long‐term immunosuppressive treatment and may develop permanent disabling weakness. In uncontrolled studies, B cell depletion with rituximab proved effective in most patients with refractory disease, inducing prolonged clinical responses associated with a sustained reduction of serum antibody levels. Promising results from experimental studies and case reports suggest that both 3,4‐diaminopyridine and albuterol may be effective as symptomatic agents. [ABSTRACT FROM AUTHOR]