HLA-DRB1/DQB1 susceptibility for autoimmune polyglandular syndrome type II and III in south of Tunisia

Objectives

The aim of our study was to investigate the association of HLA-DRB1 and HLA-DQB1 alleles with autoimmune polyglandular syndromes (APS) type II and III in a southern Tunisian population.

Patients and methods

Sixty-two unrelated patients with APSII (n = 20) and APSIII (n = 42) and 146 healthy controls were genotyped for HLA class II alleles (DRB1*, DQB1*) by PCR-SSP technique.

Results

An increased frequencies of HLA-DQB1*03:02 (P = 0,02; OR = 2.98) in APSII patients, HLA-DRB1*03 (P = 3 10⁻⁶; OR = 4.28) and HLA-DQB1*02:01 (P = 0.04; OR = 1.95) in APSIII patients were found compared to healthy controls. Study of the HLA-DRB1*;DQB1* haplotype frequencies showed a higher occurrence of DRB1*04;DQB1*03:02 and DRB1*03;DQB1*02:01 in APSII patients (P = 4 10⁻³; OR = 3.31 and P = 0.03; OR = 2.74 respectively) whereas APSIII was only associated with DRB1*03;DQB1*02:01 (P = 7.2 10⁻⁸, OR = 4.71).

Conclusion

Our data suggest that the variation in class II HLA alleles and haplotypes could be a genetic factor involved in the susceptibility of APS syndrome.     

Pulmonary non-infectious diseases in common variable immunodeficiency

Few studies have described pulmonary non-infectious diseases (PNID) in patients with common variable immunodeficiency (CVID). Indeed the most frequent complications in these patients are infectious. The aim of our study is to analyze the characteristics of PNID in a retrospective study of patients with CVID of two pneumology departments in Paris (France), from 1990 to 2008. PNID was observed in 11 patients. Mean immunoglobulin serum level was 3.46 g/L. The PNID observed were: arteriovenous pulmonary fistula: three; interstitial lung disease: three; asthma: two; mediastinal lymphadenopathy: four; emphysema: one; mesothelioma: one. Our study outlines the broad spectrum of pulmonary manifestations related to CVID. Clinicians should be aware of the diagnosis of PNID even in patients without classic infectious manifestations.     

Syndromes of resistance to TSH

The resistance to TSH action is a genetic disease characterized by molecular defects hampering the adequate transmission of TSH stimulatory signal into thyroid cells. In principle the defect may affect every step along the cascade of events following the binding of TSH to its receptor (TSHR) on thyroid cell membranes. The phenotypic expressivity of TSH resistance is highly variable going from severe congenital hypothyroidism (CH) with thyroid hypoplasia to mild hyperthyrotropinemia (hyperTSH) associated with an apparent euthyroid state. More severe forms follow a recessive pattern of inheritance and occur in patients with biallelic mutations both causing a severe loss of TSHR function. Differential diagnosis in these cases includes the exclusions of other causes of isolated thyroid dysgenesis. Mildest forms may instead occur in patients with monoallelic TSHR defects following a dominant mode of inheritance. In these cases we described the dominant negative effect exerted by some mutants on the activity of the receptor encoded by the wild type allele. In these cases, differential diagnosis involves the exclusion of autoimmune thyroid disease or pseudohypoparathyroidism associated with defects at the GNAS locus. This review will focus on the variable clinical expression of this disease.     

Relationship between the IL12B (rs3212227) gene polymorphism and susceptibility to multiple autoimmune diseases: A meta-analysis

Objectives: The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP) IL12B 3^′UTR +1188A/C (rs3212227) confers susceptibility to several autoimmune diseases.

Methods: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association.

Results: Twenty-five studies were included in the meta-analysis, which contained 9794 cases and 11,330 controls. Our result indicated that IL12B +1188A/C (rs3212227) polymorphism was associated with type-1 diabetes (T1D) in the dominant model (p?=?0.008), and an increased risk was found in East Asians in the dominant model (p?<?0.001). East Asians rheumatoid arthritis (RA) patients seemed to be at risk of allelic model (p?=?0.011). As to Behcet's disease (BD), there was a risk in dominant model (p?=?0.020) and positive associations of dominant model, allelic model in East Asians (p?=?0.009; p?<?0.001, respectively). But we failed to find any association between IL12B +1188A/C (rs3212227) polymorphism with Graves’ disease (GD) and ankylosing spondylitis (AS).

Conclusions: The present study suggests that the IL12B +1188A/C (rs3212227) polymorphism might be associated with genetic susceptibility to autoimmune diseases, such as T1D, RA, BD, but not GD and AS.