MICA gene triplet repeat polymorphism in patients with HLA-B27 positive and negative ankylosing spondylitis from Sardinia

OBJECTIVE: We investigated the distribution of MICA triplet repeat polymorphism in a random population and in patients with seronegative spondyloarthritis from Sardinia compared to continental Italy. METHODS: We analyzed the distribution of MICA triplet repeat polymorphism in HLA-B*2709 [not associated with ankylosing spondylitis (AS)] and B*2705 (associated with AS) haplotypes, to verify whether the strong association of MICA-A4 with HLA-B27 reported in other populations is maintained in Sardinia, and compared the distribution of MICA-A alleles in HLA-B27 negative versus HLA-B27+ patients with AS. RESULTS: We found that the frequency of MICA-A4 triplet repeat allele in a random Sardinia population is higher (53.2%) than in other Caucasian populations (around 20%); this allele is strongly associated with both HLA-B*2709 and B*2705. No significant difference between HLA-B27+ patients with AS and healthy controls was found: the MICA-A4 allele was present in more than 90% of subjects. MICA-A4 was found in 16 out of 20 HLA-B27 negative Sardinian patients with AS, with a frequency (80%) more similar to that of the HLA-B27+ group of patients than that of controls. CONCLUSION: The high frequency of MICA-A4 allele in HLA-B27 negative patients with AS from Sardinia, suggests the presence within the HLA region of a susceptibility factor other and certainly weaker than B27. This factor is likely to be more easily found by analyzing genetically homogeneous populations like the Sardinian, characterized by a small number of very frequent haplotypes.     

Effects of iron manipulation on trace elements level in a model of colitis in rats

AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis. METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet, iron-supplemented diet, and sham-treated controls. Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured. RESULTS: Macroscopic damage was reduced in iron-deprived groups and increased in iron-supplemented rats. Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats. CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.     

Ulcerative colitis,seronegative spondyloarthropathies and allergic diseases: the search for a link

BACKGROUND: Allergic diseases and seronegative spondyloarthropathies are frequently observed in ulcerative colitis (UC). In this report we have investigated possible relationships between IgE-mediated allergic disease (AD), allergic contact dermatitis (ACD) and seronegative spondyloarthropathy (SpA) in UC patients at different grades and extensions of mucosa inflammation. METHODS: Forty-five UC consecutive outpatients were graded according to clinical, endoscopic and histologic activity scores. SpA was diagnosed according to the European Spondyloarthropathy Study Group criteria. AD was detected by skin prick tests and confirmed by specific provocation tests, while ACD was diagnosed using the European standard series of patch tests. Thirty-seven patients' spouses or partners served as controls. RESULTS: Fourteen patients and 1 control subject showed SpA (P = 0.001). Diagnosis of rhinitis, conjunctivitis or asthma was made in 19 patients and in 5 controls (P = 0.004), while ACD was found in 10 and in 4 (P = 0.17), respectively. In UC, AD coexisted with SpA in 2 cases (P = 0.01), AD with ACD in 1 case (P = 0.03) and ACD with SpA in 5 (P = 0.24). CONCLUSIONS: Notwithstanding the high frequency of AD and SpA found in UC, the concurrence of AD with SpA or ACD is an unusual finding, while SpA and ACD may coexist. These data suggest that, in UC, atopy and seronegative arthritis, as well as atopy and delayed-type allergy, are strongly polarized conditions tending to mutual exclusion. In UC, the presence of AD without SpA or ACD, and of SpA or ACD without AD may indicate subgroups of patients in which T-helper-2 cell or T-helper-1 cell responses predominate.     

Correction to: Characteristics of taste dysfunction in COVID‑19 subjects coming from two different countries

Journal of NeuroVirology - A correction to this paper has been published: https://doi.org/10.1007/s13365-021-00976-y     

MGMT promoter methylation and correlation with protein expression in primary central nervous system lymphoma

The O ⁶-methylguanine-DNA-methyltransferase (MGMT) gene encodes for a DNA repairing enzyme of which silencing by promoter methylation is involved in brain tumorigenesis. MGMT promoter methylation represents a favorable prognostic factor and has been associated with a better response to alkylating agents in glioma and systemic lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal malignant lymphoma. The current standard of care, based on high-dose methotrexate chemotherapy, has improved prognosis but outcome remains poor for a majority of patients. Therapeutic progress in this field is conditioned by limited biological and molecular knowledge about the disease. Temozolomide has recently emerged as an alternative option for PCNSL treatment. We aimed to analyze the MGMT gene methylation status in a series of 24 PCNSLs, to investigate the relationship between methylation status of the gene and immunohistochemical expression of MGMT protein and to evaluate the possible prognostic significance of these biomarkers. Our results confirm that methylation of the MGMT gene and loss of MGMT protein are frequent events in these lymphomas (54 % of our cases) and suggest that they are gender and age related. MGMT methylation showed high correlation with loss of protein expression (concordance correlation coefficient?=??0.49; Fisher exact test: p?MGMT promoter (n?=?4), seems to be associated with a prolonged overall survival (>60 months in three of four patients). The prognostic significance of these molecular markers in PCNSL needs to be further studied in groups of patients treated in a homogeneous way.