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PubMed2006

Microsatellite typing of the human leucocyte antigen region: analytical approach and contribution to rheumatoid arthritis immunogenetic studies.

Within the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-DRB1 locus is clearly associated with rheumatoid arthritis (RA). Using a microsatellite (MSat) typing approach, we aimed to identify other loci associated with RA susceptibility and/or severity within the MHC. A panel of nine MSat HLA loci [D6S291, D6S2876 (G51152), D6S1666 (DQCAR II), D6S273, D6S2789 (TNFd), D6S2810 (MIB), D6S265, D6S2222, D6S2239], and HLA-A, -B and -DRB1 genes were typed in 170 RA cases and 282 controls. For susceptibility analysis, MSat and HLA allele distribution were compared between cases and controls, before and after stratification on HLA-DRB1*04. Haplotype frequencies were estimated using an expectation-maximization algorithm in a permutation test procedure. For severity analysis, we compared the distribution of structural damage score at onset and after 4 years of follow-up in RA cases carrying susceptibility alleles. Two MSat polymorphisms were positively associated with RA susceptibility: allele*136 of D6S265 [odds ratio, OR (confidence interval, CI) = 1.55 (1.11-2.17), P= 0.007], allele*116 of D6S2239 [OR = 1.34 (1-1.79), P= 0.03] and HLA-A2 [OR = 1.46 (1.08-1.98), P= 0.01]. Two MSat polymorphisms were negatively associated with RA susceptibility: allele*133 of D6S273 [OR = 0.3 (0.1-0.75), P= 0.005] and allele*177 of D6S291 [OR = 0.72 (0.53-0.96), P= 0.02]. The association between allele*136 of D6S265 and RA susceptibility remained unchanged after stratification on HLA-DRB1*04. The haplotypic analysis showed an overrepresentation of D6S265*136/HLA-A*02 haplotype, which suggests an effect independent of HLA-DRB1 locus in RA susceptibility. While HLA-A2 and HLA-DR4 were associated with RA severity, no MSat polymorphism was associated with structural damage score.

Arthritis, Rheumatoid↗
PubMed1976

A lymphocyte immunogenetic system, Atri, associated with the ABO blood group and the ABH secretor system.

The antigen Atri can be detected on the lymphocytes of 5.19% of A, ABH secretor individuals. The Atri substance is present in the plasma of the same individuals and can be fixed on group O erythrocytes. It is also found in the saliva of 30 out of 32 A non-secretor individuals. Its existence in the saliva of A secretor individuals, however, cannot be proved due to the presence of both the A and Atri antigens. The A AND Atri antigens have been shown to be distinct on lymphocytes by capping and by blocking of the A sites. The fact that in several families the Atri antigen is not expressed by the parents shows that its expression on lymphocytes requires the intervention of at least one gene in addition to ABO and Se.

ABO Blood-Group System↗
PubMed1977

Conceptual framework shifts in immunogenetics. I. A new look at cis AB antigens in the ABO system.

The so-called 'cis AB' blood group is accounted for by proposing that 'normal' anti-A and anti-B reagents are cross-reacting with partially overlapping reaction ranges. Hence, they are labelled anti-AX and anti-BX, respectively. Some consequences of a complex-simple model where 'cis AB' is accordingly produced by a simple (mono-factorial) antigen X (produced a simple gene X at the ABO-locus) are briefly explored.

ABO Blood-Group System↗
PubMedDate not supplied

Conceptual framework shifts in immunogenetics. II. Some notes on the Ag system.

Two Caucasian population materials totalling 530 individuals and 3,180 typing results are analyzed with regard to various combinations of the Ag(x, y, a1, d, c, g) factors. Superficially, both materials appear well aligned to each other and the contemporary (simple-complex) framework. However, when the same set of data are structuralized within a new (complex-simple) framework, the typing results for 12 of 362 or 3.3% of the Swiss and no less than 19 of 168 or 11.3% of the English samples are not compatible with the new framework specifying that the various anti-Ag reagents can be arranged in two 'inclusion groups'--the anti-Ag (y greater than d greater than c) and the anti-Ag (g greater than a1 greater than x) series.

England↗
PubMed2005

Myasthenia gravis accompanied by alopecia areata: clinical and immunogenetic aspects.

The purpose of this study was to evaluate the clinical characteristics of patients who had both myasthenia gravis (MG) and alopecia areata (AA). Clinical information was retrospectively collected for 159 Japanese patients with MG. Human leukocyte antigen (HLA)-DQB1 and DRB1 alleles were determined by genotyping. Of 159 MG patients, six (3.7%) developed AA after the onset of MG and thymectomy. The prevalence of AA in MG patients was higher than that reported in Caucasians. The frequencies of bulbar involvement, myasthenic crisis, and thymoma were significantly higher in MG patients with AA than in those without (P = 0.007, 0.004, and 0.006, respectively). All but one patient with AA had advanced stage thymoma. Three patients with a severe form of AA (alopecia totalis) had additional autoimmune diseases: myocarditis, myositis, and pure red cell aplasia. DRB1*0901 and DQB1*0303 tended to be more frequently detected in the six MG patients with AA than in the 82 patients without it. In conclusion, a subset of MG patients who have severe neuromuscular symptoms and thymoma develop AA several years after thymectomy.

Adolescent↗
PubMed1975

Immunogenetics of the Lennox-Gastaut syndrome: frequency of HL-A antigens and haplotypes in patients and first-degree relatives.

Twenty-two patients with the Lennox-Gastaut syndrome and their families were examined for HL-A antigens by the microlymphocytotoxicity test. The antigen HL-A7 belonging to the HL-A locus showed a significantly increased frequency (p less than 0.0005) both in parents and in patients. The same antigen showed a significantly altered segregation in patients but a normal one in healthy siblings. Another antigen of the second HL-A locus, HL-A12, did not display a normal segregation in our patients, in whom it was nearly not represented.

Epilepsy↗
PubMed1990

Immunogenetic aspects of human thyroglobulin-reactive T cell lines and hybridomas.

The in vitro proliferative response to T cells primed with human thyroglobulin (Tg) was compared in 11 independent haplotypes on B10 background. B10.K and B10.S mice were the most responsive, whereas, with the exception of B10.PL (H-2u), all other B10 congenics were intermediate responders. The two best responders to in vitro challenge with human Tg, of the k and s haplotype, are the same as those showing H-2-linked susceptibility to induction of experimental autoimmune thyroiditis (EAT) with mouse Tg. Since shared epitopes on human and mouse Tgs have been shown to be thyroiditogenic by adoptive transfer studies in CBA (H2k) mice, the findings indicate that shared epitopes may be studied in appropriate (i.e. EAT-susceptible) strains of mice. Therefore, we proceeded to develop methods to produce T-cell lines and hybridomas to human Tg in B10.K and B10.S mice, test their cross-reactivity to heterologous Tgs and their Ia restriction patterns. By using antigen-presenting cells from recombinant strains, we identified restriction elements encoded by the I-A subregion alone and a combinatorial molecule from the I-A/I-E subregions.

Animals↗