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The competitive binding between CpG-ODN (single-stranded DNA from pathogens) and HLA-B and HLA-A ligands for the inhibitory Killer Immunoglobulin-like Receptors (KIR)3DL1/2 may lead to possible hypo-sensing of pathogens and ineffective clearance. We observed an overabundance of HLA ligands for inhibitory KIR with three domains in KD subjects.

Problem To target gestational diabetes mellitus (GDM) by means of temporal variation in pregnancy-associated plasma protein A (PAPP-A) and soluble human leukocyte antigen-G (sHLA-G). Method of study Retrospective analysis of PAPP-A and sHLA-G blood levels in historical samples of 112 GDM and 112 controls, drawn at first trimester, and prospective study in 18 GDM and 105 controls collected in triplicate along the pregnancy. Six hundred and sixty-five samples were analyzed. Results Gestational diabetes mellitus had significantly lower first-trimester PAPP-A concentrations than controls (2343 ± 1519 versus 2996 ± 1955 mU/mL, in retrospective brunch and 2490.57 ± 1828.52 versus 3240.84 ± 1930.69 mU/L in prospective one, P

Birth weight is known to be a direct indicator of perinatal mortality and a clear predictor of adult pathologies too. It has been correlated with several causes of mortality in adulthood: low birth weight with diabetes, nephropathy and cardiovascular diseases and high birth weight with autoimmune diseases and cancer. In genome-wide studies, an extended human leucocyte antigen (HLA) region has been linked to birth weight variation. We focused our attention on the HLA haplotypes marked by HLA-A, HLA-B and HLA-DRB1 polymorphisms in 1206 healthy Caucasian newborns belonging to the Cord Blood Bank of Pavia (Italy) and their mothers, aiming to investigate the association between this restricted HLA region and birth weight variation. In our study, the HLA-B*38;DRB1*13 haplotype showed an ascending trend among centiles addressing to the high foetal weight. The HLA-A*02;B*15 haplotype showed a descending trend among centiles addressing to the low foetal weight. Besides the acknowledged correlation between the HLA-A*02 and HLA-B*15 alleles (as well as low birth weight) and type I diabetes and between the HLA-B*38 and HLA-DRB1*13 alleles (as well as high birth weight) and several autoimmune diseases, we cannot predict if our babies, healthy at birth, will suffer from these pathologies during life. Nevertheless, our data point to the HLA telomeric end for markers linked to the low birth weight and to the HLA centromeric end for markers linked to the high birth weight, thus limiting the region involved in birth weight variation, which still represents a useful predictor of disease risk in adulthood.

In utero selection processes are probably related to mother-father compatibility as has been reported in abortion-prone couples and in Down syndrome studies. In order to analyse this phenomenon, we investigated families with chromosomal imbalance (Turner syndrome). We chose this model because previous data indicated a high frequency of HLA-A31 and B38 in Turner patients and in their mothers. We report high HLA antigen sharing in Turner families and great histocompatibility between mother and affected daughter, not related to abortion histories. The proportion of HLA-A homozygous cases among Turner children was higher than expected. The level of lymphocytotoxic antibodies against fetus in mothers of Turner patients was comparable to that of mothers of families with normal fertility and probably favoured these pregnancies.

To assess the occurrence of growth hormone deficiency (GHD) in patients with coeliac disease (CD).A total of 1066 children diagnosed elsewhere with short stature were referred to our centre for second-line evaluation in a 6-year period. All patients were screened for CD by antiendomysial antibodies (EMA) and those with positive sera underwent intestinal biopsy.Among the 1066 short children, 210 (19.7%) had GHD and 12 (1.12%; chronological age from 3.6 to 12.3 years, bone age from 1.5 to 10.5 years, SDS height from -3.05 to -0.48), having positive EMA, showed histologically confirmed CD. Nine of these latter 12 CD children had a beneficial effect on growth rate after the first year of gluten-free diet, while the remaining three showed no catch-up growth. A careful endocrinological investigation in these three CD boys showed an isolated GHD in two cases and a multiple GHD in one case. The congenital origin of GHD is supported by the congenital abnormalities documented by magnetic resonance imaging. GH therapy associated with gluten-free diet led to an increased growth rate.GH secretion should be evaluated in coeliac patients showing no catch-up growth after a period on a gluten-free diet in spite of reversion to seronegativity for EMA. In the case of GHD and CD, replacement GH therapy should be started during a gluten-free diet.

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

OBJECTIVE Following the observation of two patients affected by true precocious puberty who went on to develop polycystic ovary syndrome (PCOS) and who were found to be heterozygotes (carriers) for 21-hydroxylase deficiency (21-OHD), we decided to evaluate the frequency of heterozygosity for adrenal 21-OHD in patients with true precocious puberty. STUDY DESIGN We investigated 32 girls affected by true precocious puberty, by the single-dose ACTH stimulation test, HLA typing and the molecular analysis of the CYP21B gene encoding for the 21-OH enzyme, in order to detect gene deletions or point mutations. Twenty-eight cases were on LHRH analogue treatment and the remaining four, untreated owing to parental refusal, were investigated 0.5–1.5 years after spontaneous menarche. RESULTS After ACTH testing, 13 out of the 32 (41%) cases displayed higher 17-hydroxyprogesterone (17-OHP) levels than normal but less than those found in patients affected by nonclassical adrenal hyperplasia (CAH); these levels were similar to those observed in obligate heterozygotes for CAH due to 21-hydroxylase deficiency (21-OHD). HLA typing showed a significantly increased frequency of the HLA alleles A28 and B14 which are peculiar to the HLA haplotypes of nonclassical CAH due to 21-OHD. Molecular analysis of the CYP21B gene showed that in four out of the 10 tested patients with an exaggerated 17-OHP response there were heterozygous point mutations of the CYP21B gene. In contrast, no CYP21B gene abnormalities were detected in the eight tested patients with normal 17-OHP. No differences were found between carriers and non-carriers of the 21-OHD with regard to age at onset of precocious puberty, clinical features, bone age acceleration and gonadal suppression induced by LH-RH analogue treatment. Two out of the four untreated patients who were investigated after menarche were found to be carriers of the 21-OHD; these girls showed signs of androgen excess, irregular menses and polycystic ovaries. CONCLUSIONS A high frequency of heterozygosity for adrenal steroid 21-OHD was found in our patients with true precocious puberty. This adrenal defect does not seem to influence the pattern of central precocious puberty, but these patients require long-term follow-up as they might go on to develop polycystic ovary syndrome (PCOS). Whether or not heterozygosity of the 21-OHD may be related to the premature activation of the hypothalamo-pituitary-gonodal axis remains to be defined.