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Background: During the last decade, vitamin D (VitD) has become a topic of interest in immune regulation, especially in multiple sclerosis (MS) disease. Amongst the wide range of effects reported for this vitamin on the immune system, a regulatory role on cytokines production has been described. Our aim is to analyze the status of VitD and its correlation with the circulating inflammation and the intrathecal humoral response during MS. Methods: We analyzed samples of 318 individuals: 108 MS patients and 210 controls. Determination of 25-(OH) VitD3 level in serum was made using electrochemiluminescence method. Circulating inflammatory cytokines (IL-6, IL-8, IL-10, TNF-a, IL12p70 and IL-1b) were investigated using Cytometer Bead Array Technology. The central humoral response was characterized using CSF isofocusing test and IgG Index calculation. Results: As expected, mean value of VitD was significantly lower in MS group (26 nmol/L) than in control group (34.75 nmol/L) (p=0.002), with a severe deficiency in 67% of MS patients. Mean value of VitD was significantly lower in MS female patients. Regarding cytokines, mean value of TNFa was significantly higher in MS patients with oligoclonal bands of IgG in the CSF. IL6 was positively correlated with IgG level in serum of MS patients. Conclusions: Our results support the association of VitD deficiency with MS, especially in female patients of our region. However, the vitamin level seems to not correlate with inflammatory cytokines nor with disability. Interestingly, TNFa and IL6 levels were correlated with the intrathecal synthesis of IgG and the circulating IgG level, respectively.

Objective Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. Methods We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. Results A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 10.87 years [range, 45–90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. Conclusion BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM. [ABSTRACT FROM AUTHOR]

The inducible T‐cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen‐presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case–control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (−693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)‐restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p =.001, odds ratio [OR] = 2.18 IC [1.36–3.49]); codominant genetic model 2, (C/C vs. T/T) p =.007, OR = 15.29 IC [1.97–118.5]); dominant genetic model, (C/C vs. C/T + T/T) p =.0001, OR = 2.44 IC [1.53–3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p =.016, OR = 0.08 IC [0.01–0.63] and p = 7.6904E − 05, OR = 0.43 IC = [0.28–0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti‐SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus (PF) is a bullous autoimmune skin disease diagnosed through sera and skin analyses. PF severity is associated with maintained anti‐Dsg1 sera levels and its prognosis is unpredictable. MicroRNA (miRNA), dynamic regulators of immune function, have been identified as potential biomarkers for some autoimmune diseases. This study aimed to assess the miRNA expression of miR‐17‐5p, miR‐21‐5p, miR‐146a‐5p, miR‐155‐5p and miR‐338‐3p using quantitative real‐time PCR in peripheral blood mononuclear cells (PBMC) and lesional skin samples from untreated and treated PF patients (both remittent and chronic) over 3 months. Overall, miRNA expression was significantly higher in PBMC than in biopsy samples. Blood miR‐21 expression was increased in untreated patients compared to controls and had a diagnostic value with an AUC of 0.78. After 6 weeks, it decreased significantly, similar to anti‐Dsg1 antibodies and the PDAI score. In addition, a positive correlation was observed between cutaneous miR‐21 expression and the disease activity score. Conversely, cutaneous expressions of miR‐17, miR‐146a and miR‐155 were significantly higher in treated chronic patients compared to remittent ones. The cutaneous level of miR‐155 positively correlated with pemphigus activity, making it a potential predictive marker for patients' clinical stratification with an AUC of 0.86.These findings suggest that blood miR‐21 and cutaneous miR‐155 can be used as supplemental markers for PF diagnosis and activity, respectively in addition to classical parameters. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii (T. gondii) causes toxoplasmosis, a dangerous and prevalent disease. Toll-like receptors (TLRs) are the best-studied pattern recognition receptors in mammals. Objective: The current study was conducted at Al-Diwaniya Maternity and Children Teaching Hospital, Diwaniyah city, Iraq, from December 2020 to August 2021. Methods: Blood samples and placenta tissue pieces were collected prospectively from 30 patients newly diagnosed with toxoplasmosis and 64 healthy controls. Women in both groups underwent a spontaneous abortion. A human Toll-Like Receptor 4 (TLR4) ELISA kit was used to measure TLR4 levels and blood DNA extraction. ARMS-PCR was adopted to analyze the polymorphism for TLR4 Asp299Gly, and SAG3 marker was used to analyze the genotype of Toxoplasma strains. Results: The frequency distribution of the A allele and G allele was statistically non-significant between the patients and the control group. The polymorphism analysis of the Asp299Gly SNP in the TLR4 gene showed abortion had no significant association with toxoplasma infection (P> 0.05). Genotype II was more prevalent in aborted Iraqi women (22/30) than in control. The obtained result revealed that the concentration of TLR4 in serum women infected with type I Toxoplasma was significantly higher (P< 0.05) in the AA genotype of TLR4 Asp299Gly (mean 1328 pg/ml, SD: 266.1pg/ml), compared to AG genotype (mean; 923.6 pg/ml, SD: 27.2 pg/ml). Discussion: These findings highlighted the significance of TLR molecules in Toxoplasma gondii infection and the need for close collaboration between practitioners and to lessen the illness burden of toxoplasmosis. [ABSTRACT FROM AUTHOR]