Thyroid autoimmunity in relation to HLA-DRB1 and HLA-DQB1 polymorphism in nonsegmental vitiligo: a cross-sectional-study.

OBJECTIVES: Nonsegmental vitiligo (NSV) is frequently associated with thyroid autoimmunity (TAI), however, the immunopathogenic mechanisms of such association remain to be investigated. The aims of this work were to estimate the frequency of TAI and to describe the genetic polymorphism in the human leukocyte antigen (HLA)-DRB1 and -DQB1 loci in TAI susceptibility among patients with NSV. PATIENTS AND METHODS: In this cross-sectional study, screening for TAI was performed in 97 Moroccan patients with NSV by measuring antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb). HLA-DRB1 and -DQB1 were determined with single specific primer-polymerase chain reaction (PCR-SSP) typing methods. RESULTS: TAI was diagnosed in 20 patients with NSV (20.6%). The phenotypic frequency of DQB1*05 (OR = 5.04; P = 0.006; pc = 0.036) was significantly higher in NSV patients with TAI. Genotype DQB1*05/DQB1*06 (OR = 25.33; P = 0.001; pc = 0.003) confer susceptibility to TAI in NSV patients. NSV patients with TAI and early onset vitiligo have an extremely high phenotype frequency of DQB1*05 allele (OR = 14.67; P = 0.001; pc = 0.048) and DQB1*05/DQB1*06 genotype (OR = 26.55; P = 0.01; pc = 0.03). TAI in patients with NSV was (6.2%) associated with onset of clinical thyroid disease based on TSH and free T4. CONCLUSION: Our findings suggest that HLA-DQ polymorphisms influence TAI risk in subjects with NSV, although HLA does not completely explain the co-occurrence of these two diseases.

IL-1RA autoantibodies: insights into mechanisms and associated diseases.

The association of neutralizing autoantibodies targeting interleukin-1 receptor antagonist (IL-1RA) with multisystem inflammatory syndrome, IgG4-related disease, and vaccine-related myocarditis is increasingly recognized. The detection of IL-1RA autoantibodies can be notably affected by the techniques and methods employed. Two categories of assays are available: solid-phase immunoassays, which detect binding of IL-1RA autoantibodies, and functional IL-1 signaling reporter cell assays, which offer greater specificity by determining whether circulating autoantibodies can impede interleukin (IL)-1ß signal transduction pathways. It is as yet unclear why only a minority of individuals produce pathogenic anti-IL-1RA autoantibodies in response to coronavirus disease 2019 (COVID19) or vaccination. This review article discusses our current knowledge of the process of IL-1RA autoantibody generation, the underlying pathogenesis, detection, and potential treatment strategies for associated diseases.

Multifaceted roles of Fcγ receptors in COVID-19 and vaccine responses.

Recent data have revealed various effector functions of FcγRs in immune responses against challenges with SARS-CoV-2 virus. FcγRs act as a bridge between antibody specificity and effector cells. In many cases, IgG/FcγR interactions generate cell-mediated immune protection from infection via ADCP or ADCC. These responses are beneficial, as they may participate in virus elimination and persist longer than neutralizing anti-Spike antibodies. In contrast, these interactions may sometimes prove beneficial to the virus by enhancing viral uptake into phagocytic cells via ADE and causing excessive inflammation. Here, we summarize key features of FcγRs, discuss effector functions, clinical relevance, and factors influencing FcγR-mediated immune responses in COVID-19 and vaccine responses, and consider IVIg and kinase inhibitors for targeting FcγRs signaling in COVID-19.

Prevalence of liver fibrosis and cirrhosis in 699 Moroccan patients with chronic hepatitis C.

INTRODUCTION: chronic hepatitis C (CHC) can cause severe complications, including fibrosis and cirrhosis. Very little is known about the prevalence of these complications in the Moroccan population. METHODS: the prevalence of liver fibrosis and cirrhosis using a non-invasive blood test (FibroTest and ActiTest) was studied in 699 Moroccan patients with CHC for 4 years (from January 2014 to December 2017). The serum immunological markers: α2-macroglobulin, haptoglobin, apolipoprotein A1 were analyzed nephelometrically on BN ProSpec® System. The serum biochemical markers: γ-glutamyltransferase, alanine aminotransferase, and bilirubin were performed using the VITROS® Chemistry System Ortho Clinical Diagnostic. A 699 patients with CHC were identified. RESULTS: the overall prevalence of cirrhosis (F4) was estimated at 31.8%. Thirteen point nine percent (13.9%) of patients with cirrhosis had a risk of developing esophageal varices and a 3.3% risk of developing primary liver cancer. The association between cirrhosis and age showed an increase in prevalence after age 55 years old [OR=7.68(95%CI=4.9-12.2); p<0.0001]. No significant association for cirrhosis was found for sex. CONCLUSION: according to the results of FibroTest, 32% of patients with CHC had cirrhosis. The older age was independently associated with liver cirrhosis.

Features of HLA class I expression and its clinical relevance in SARS-CoV-2: What do we know so far?

Modifications in HLA-I expression are found in many viral diseases. They represent one of the immune evasion strategies most widely used by viruses to block antigen presentation and NK cell response, and SARS-CoV-2 is no exception. These alterations result from a combination of virus-specific factors, genetically encoded mechanisms, and the status of host defences and range from loss or upregulation of HLA-I molecules to selective increases of HLA-I alleles. In this review, I will first analyse characteristic features of altered HLA-I expression found in SARS-CoV-2. I will then discuss the potential factors underlying these defects, focussing on HLA-E and class-I-related (like) molecules and their receptors, the most documented HLA-I alterations. I will also draw attention to potential differences between cells transfected to express viral proteins and those presented as part of authentic infection. Consideration of these factors and others affecting HLA-I expression may provide us with improved possibilities for research into cellular immunity against viral variants.

Innate immune evasion by SARS-CoV-2: Comparison with SARS-CoV.

SARS-CoV-2 virus, a member of the Coronaviridae family, causes Covid-19 pandemic disease with severe respiratory illness. Multiple strategies enable SARS-CoV-2 to eventually overcome antiviral innate immune mechanisms which are important components of viral pathogenesis. This review considers several mechanisms of SARS-CoV-2 innate immune evasion including suppression of IFN-α/ß production at the earliest stage of infection, mechanisms that exhaust natural killer cell-mediated cytotoxicity, overstimulation of NLRP3 inflammasome and induction of a cytokine storm. A comparison with SARS-CoV is made. Greater knowledge of these and other immune evasion tactics may provide us with improved possibilities for research into this novel deadly virus.

Concomitant primary hyperparathyroidism and systemic lupus erythematosus: coincidence or not? A new case report.

Primary hyperparathyroidism (PHP) is the most common cause of hypercalcemia. Patients with systemic lupus erythematosus (SLE) can develop hypercalcemia but it is exceptionally due to PHP. There are only few cases of concurrent SLE and primary hyperparathyroidism (PHP) described in the literature. We report a case of a 31-year-old patient having SLE with lupus nephritis class III and anti-phospholipid syndrome, complicated by pulmonary embolism associated to primary hyperparathyroidism causing severe hypercalcemia and osteoporosis. Even if there is no evidence for potential pathogenic association between PHP and SLE, the recognition of this association is very important because of therapeutic and prognostic impact. Early detection of PHP leads to avoid severe complications and significant morbidity.

Moroccan study of HLA (-A, -B, -C, -DR, -DQ) polymorphism in 647 unrelated controls: Updating data.

The scope of this study is to investigate the HLA (Human Leukocyte Antigen) distribution and polymorphism in a large sample of healthy Moroccans in order to extend and update the available data. 647 unrelated Moroccan controls originating from diverse regions of the country were typed using microlymphocytotoxicity for HLA-A and -B, sequence-specific-primer amplification for -C, -DR, and -DQ and Luminex HD for specific -DR. The most frequent allele groups detected were HLA-A2 (19.2%), -B44 (12.4%), -C*07 (24.4%), -DRB1*03 (16.9%), -DRB1*04 (18.4%), -DQB1*02 (28.7%) and -DQB1*03 (27.8%). The most predominant specific alleles found for DRB1 were: *03:01, *04:02, *04:05, *07:01, *11:01, *13:02 and *15:01. Rare allelic variants were detected, for the first time in Moroccan population, at the DRB1*03 (*03:52, *03:54, *03:56), DRB1*07 (*07:07, *07:11, *07:16) and DRB1*11 (*11:70) locus. The most frequent haplotypes were: A2-B44, A30-B18, A2-C*16, A30-C*06, B14-C*08, B58-C*07, B45-C*06, DRB1*03-DQB1*02, DRB1*04-DQB1*03, DRB1*07-DQB1*02 and DRB1*15-DQB1*06. Comparison of genetic distances and haplotypes with other populations shows that the Moroccans are genetically closer to North Africans and Europeans than to sub-Saharan Africans. Our results reflect the high degree of HLA polymorphism in the Moroccan population and provide a useful baseline of healthy Moroccan controls for disease association and anthropological studies.

Dietery factor obesity microenvironnement and breast cancer.

BACKGROUND: Breast cancer is a multifactorial disease. Factors most often mentioned risks are those related to the environment, genetics, hormones and individual behaviors. Among these include alcohol, smoking, sedentary lifestyle and eating habits. Identification of eating and the role of nutritional factors may be involved in cancer risk have been studied extensively since nearly 40 years. PURPOSE: We conducted a study of breast cancer type case-control with food frequency questionnaire to assess the causal relationship between dietary factor, obesity and breast cancer risk. PATIENTS AND METHODS: female patients with breast cancer were compared to healthy controls at the National Institute of Oncology of Rabat during 2008-2010 and were interviewed for epidemiological information and for their eating habits. RESULTS: A total of 800 women were included in this study (400 cases and 400 controls). Result of univariate analysis showed that significant factors associated with the etiologie of breast cancer: high body mass index (BMI) [odds ratio (OR) =1.30; 95% confidence interval (CI), 1.25-1.37], red meat (OR =1.33; 95% CI, 1.27-1.40), processed meat (OR =1.44; 95% CI, 1.35-1.54), eggs (OR =1.20; 95% CI, 1.14-1.23), poultry (OR =0.70; 95% CI, 0.60-0.80), fish (OR =0.67; 95% CI, 0.61-0.73), fruit (OR =0.67; 95% CI, 0.62-0.72), and vegetable (OR=0.72; 95% CI, 0.67-0.78). Multivariate analysis indicated that a significantly elevated risk of contracting breast cancer was associated with higher BMI (OR =9.61; 95% CI, 6.1-15.15), red meat (OR =4.61; 95% CI, 2.26-9.44) and processed meat (OR =9.78; 95% CI, 4.73-20.24). In contrast consumption of fish (OR =0.07; 95% CI, 0.02-0.24), poultry (OR =0.61; 95% CI, 0.46-0.81), fruit (OR =0.001; 95% CI, 0.00-0.004), and vegetable (OR =0.82; 95% CI, 0.22-3.08) remained as significant beneficial factor associated with breast cancer. CONCLUSIONS: This study is rather in favour of positive association between obesity, consumption of food rich in fatty matter and breast cancer, which is consistent with data from the literature using the same type of investigation. These results encourage increased cohort studies, case-control and experimentation in order to achieve a genuine code of cancer prevention, to define with precision the positive and negative.

Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients.

INTRODUCTION: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. METHODOLOGY: Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. RESULTS: The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. CONCLUSIONS: TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.

Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case-control study.

The aim of this study was to identify HLA class II alleles that may be involved in vitiligo genetic susceptibility in the Moroccan population and to determine susceptible and protective HLA alleles/haplotypes in vitiligo. One-hundred unrelated vitiligo patients and 300 healthy unrelated controls were studied for HLA class II alleles by polymerase chain reaction-sequence-specific primers. The phenotypic frequency of DRB1*07 (OR = 2.23, p c = 0.014) was significantly higher, while that of DRB1*03 (OR = 0.40, p c = 0.014) was significantly lower in patients than in controls. Haplotype DRB1*07-DQB1*02 (OR = 2.25, p c = 0.024) was positively associated with vitiligo patients, while haplotype DRB1*03-DQB1*02 (OR = 0.35, p c = 0.012) was negatively associated with this group. Vitiligo patients with positive family history and negative anti-thyroid peroxidase antibody (anti-TPO) have an extremely high phenotype frequency of DRB1*07-DQB1*02 haplotype (OR = 2.91, p c = 0.048 and OR = 2.62, p c = 0.00475, respectively). DRB1*03-DQB1*02 (OR = 0.32, p c = 0.048 and OR = 0.38, p c = 0.048, respectively) was negatively associated with patients without a family history and negative anti-TPO. This study demonstrated the positive association of HLA class II alleles and haplotypes with vitiligo in the Moroccan population. There may be differences in HLA haplotypes distribution in patients according to family history and anti-TPO profile.