HLA-DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies

Through a retrospective analysis of a real-life cohort of children with celiac disease (CD), who underwent HLA-DQ genotyping, we supported our previous findings indicating the presence of HLA-DQB1*02 allele in at least 90%–95% of pediatric patients. In the present study, reporting the HLA-DQ analysis from 184 children (age range: 1–16 years) diagnosed with CD in a single centre, we found that 97.29% of all these CD children (n = 179 out of 184 genotyped patients) resulted to be carriers of at least one copy of HLA-DQB1*02 allele. If a widened screening for CD should result to be appropriate in the pediatric population after further clinical research, this observation might be potentially exploited to consider a two-step screening strategy, starting with the HLA-DQB1*02 targeted analysis followed by the specific serology for CD in these predisposed patients only. However, additional and larger studies are needed to support our findings

The Involvement of HLA Class II Alleles in Multiple Sclerosis: A Systematic Review with Meta-analysis

Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.</jats:p

Birth-weight as a risk factor for cancer in adulthood: the stem cell perspective.

The 'stem cell burden' hypothesis represents a plausible explanation for the association between birth-weight and the risk of breast cancer in adulthood. The size of the overall stem cell pool would be expected to affect organ size and consequently birth-weight, making birth-weight a proxy for the overall number of fetal stem cells. As stem cells are self-renewing, the greater their number is at birth, the higher will be the chance that one of them will undergo carcinogenesis over the years. To investigate the correlation between birth-weight and stem cell burden, we examined the cord blood hematopoietic CD34+ stem cell population as an indicator of the overall fetal stem cell number. We measured both the CD34+ level (by flow cytometry) and the CD34+ proliferative potential (by the GM-CFU culture), in a sample of 1037 healthy newborn cord blood donors. We found that heavier babies had a significantly greater CD34+ stem cell concentration (p < 0.001) and a higher GM-CFU number than lighter babies (p < 0.001). Thus, a high birth-weight was positively associated with a high concentration of CD34+ stem cells and also with a qualitatively higher "stemness" of this pool. Therefore, our data support the theory that birth-weight reflects the number of fetal stem cells

Global Meta-Analysis on the Association between Behcet Syndrome and Polymorphisms from the HLA Class I (A, B, and C) and Class II (DRB1, DQB1, and DPB1) Genes

Behcet syndrome (BS) is a multisystemic perivasculitis whose genetic susceptibility is linked to HLA region. We first meta-analysed all HLA class I and II genes involved in BS susceptibility in all ethnic groups worldwide. We identified 1141 articles and finally included 31 case-control studies after multiple rounds of selection. We analysed frequencies for 24 HLA-A alleles (3 alleles for HLA-A∗26 at four digits), 50 HLA-B alleles (11 alleles for HLA-B∗51 at four digits), 15 HLA-C alleles, 16 HLA-DRB1 alleles, 6 HLA-DQB1 alleles, and 15 HLA-DPB1 alleles. We meta-analysed only HLA allelic frequencies from at least three studies; therefore, we investigated 21 alleles out of 140. Going from 7.00 to 1.6 OR, we found 11 class I alleles conferring risk for BS: B∗51:08, B∗51, B∗51:01, B∗51:02, DQB1∗03, A∗26:01, Cw∗14, Cw∗15, Cw∗16, B∗15, and A∗26. Overall, the studies included populations from Europe (Greece, Spain, Italy, Germany, and Ireland), Asia (Korea, China, China Han, and Thailand), Middle East (Israel, Saudi Arabia, and Iran), and Morocco (as no other North-African population was included). We collected a number of ethnical groups sufficient to conduct an ethnic-specific meta-analysis where Europeans showed 11.25 OR for B∗51:08 and Japan 3.50 OR for A∗26:01. A remarkable result was that the most frequent HLA−B∗51 two-digit alleles associated with BS were different among populations: HLA−B∗51:08 in Europe, HLA−B∗51:01 in Turkey, and HLA−B∗51:02 in Japan. Overall, we discussed our real-world results with other imputation studies

Birth-weight as a risk factor for cancer in adulthood: the stem cell perspective.

The 'stem cell burden' hypothesis represents a plausible explanation for the association between birth-weight and the risk of breast cancer in adulthood. The size of the overall stem cell pool would be expected to affect organ size and consequently birth-weight, making birth-weight a proxy for the overall number of fetal stem cells. As stem cells are self-renewing, the greater their number is at birth, the higher will be the chance that one of them will undergo carcinogenesis over the years. To investigate the correlation between birth-weight and stem cell burden, we examined the cord blood hematopoietic CD34+ stem cell population as an indicator of the overall fetal stem cell number. We measured both the CD34+ level (by flow cytometry) and the CD34+ proliferative potential (by the GM-CFU culture), in a sample of 1037 healthy newborn cord blood donors. We found that heavier babies had a significantly greater CD34+ stem cell concentration (p < 0.001) and a higher GM-CFU number than lighter babies (p < 0.001). Thus, a high birth-weight was positively associated with a high concentration of CD34+ stem cells and also with a qualitatively higher "stemness" of this pool. Therefore, our data support the theory that birth-weight reflects the number of fetal stem cells

Correlation between {HLA}-{DQB}1{ast}06:02 and narcolepsy with and without cataplexy: approving a safe and sensitive genetic test in four major ethnic groups. A systematic meta-analysis

we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians