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L I Sakkas

Publications and source records attributed to L I Sakkas.

27 records · Page 2Linked to original sources
PubMed1990

HLA class II and T cell receptor gene polymorphisms in psoriatic arthritis and psoriasis.

HLA-DRB, DQA and DQB genes as well as the T cell receptor (TcR) alpha, beta, and gamma genes were studied by Southern blot analysis of genomic DNA from patients with psoriatic arthritis (PsA) and psoriasis alone (Ps). A subtype of DR7, DR7a, was found in 38.8% of patients with PsA, 41.5% of patients with Ps, and in 8% of healthy individuals (N) (PsA vs N: pc = 0.0002, RR = 7.1; Ps vs N: pc = 0.0002, RR = 7.9). No association with TcR genes was found. Our findings suggest either that the DR7a allele may be in linkage disequilibrium with HLA-Cw6 or that it may be an important susceptibility factor for PsA and Ps.

Adult↗
PubMed1989

Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) patients and controls.

Despite extensive analysis of the incidence of HLA-DR and HLA-DQ allele frequencies in defined autoimmune disease groups, there is very little information available on HLA-DP allele frequencies. This is largely because HLA-DP typing has until recently been restricted to primed lymphocyte typing (PLT). However, allelic polymorphism of the HLA-DP subregion can now be studied by Southern blot analysis or genotyping with DPA1 and DPB1 probes. By direct counting of allele-specific DNA fragments, we have analyzed the frequencies of five major DP genotypes (DPw1, DPw2, DPw3/6, DPw4, and DPw5), in a large number of Caucasoid rheumatoid arthritis (RA) patients (n = 74), and controls (n = 91). The predicted frequency of DP alleles in both patient and control groups was comparable to PLT-determined DP allele frequencies in normal Caucasoids. However, the gene frequency of DPw4 was increased in the RA patients, with 51% of the patients studied scoring as DPw4, 4 homozygotes. With the exception of one possible combination (DPw5 and DRw6) in the controls, no significant linkage disequilibrium was detected between DP and DR alleles in either patient or control groups. Thus the prevalence of DPw4 in the RA patients is independent of any disease association with the DR loci, and may represent a new class II association with RA.

Arthritis, Rheumatoid↗
PubMed1989

HLA-DQ beta 3.1 allele is a determinant of susceptibility to DR4-associated rheumatoid arthritis.

Rheumatoid arthritis is associated with HLA-DR4 in several ethnic groups. Since DR4 haplotypes encode a diverse array of class II molecules, it is of interest to characterize the nature of the primary association. We have examined molecular polymorphisms of HLA class II gene products expressed by normals and rheumatoid arthritis patients using monoclonal antibodies and two-dimensional electrophoresis. Most homozygous DR4 rheumatoid arthritis patients express DR beta 1 molecules associated with Dw4 or Dw14 mixed lymphocyte culture determinants. In Caucasoids, two DR4-linked DQw3-associated beta-chain alleles are defined by two-dimensional electrophoresis. These variants, designated DQ beta 3.1 and 3.2, are associated with the serologic determinants DQw7 and DQw8, respectively. A panel of 40 DR4-positive normals was also examined for nucleotide sequence polymorphisms associated with DQB3.1 and 3.2 genes using the polymerase chain reaction and specific oligonucleotide probes. At the DQ beta level the rheumatoid arthritis panel was distinguished by enrichment for the DQ beta 3.1 allele with 100% of patients positive for DQw7. Results presented here suggest that specific DQ beta alleles may modify the effect of HLA-DR4 beta 1 alleles in conferring susceptibility to rheumatoid arthritis in a phenotype-specific fashion.

Antibodies, Monoclonal↗
PubMed1989

HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major susceptibility locus within the HLA class II region.

Susceptibility to rheumatoid arthritis (RA) may be due to the presence of shared functional epitopes common to the HLA-DR beta chains of several RA-associated haplotypes. We have obtained direct evidence for this hypothesis by using the polymerase chain reaction and sequencing the DRB1 and DQB1 genes from RA patients. A highly conserved epitope present on DR beta chains of DR4 and DR1 haplotypes was found in 83% of 149 patients with classical or definite RA but was found in only 46% of 100 control individuals (P less than 0.0001). Two Dw subtypes of DR4 (Dw4 and Dw14) were associated with disease susceptibility but two other subtypes (Dw10 and Dw13) were not. Sequence differences between these subtypes implicate those residues around the putative antigen binding site of the DR beta molecule in the pathogenesis of RA. These data provide a basis for understanding host susceptibility to RA at a molecular level.

Alleles↗
PubMed1988

Arthritis in patients with psoriasis is associated with an immunoglobulin gene polymorphism.

Using a DNA probe for the switch region of immunoglobulin heavy chain genes, together with the restriction endonuclease Sst I, we detected a particular polymorphic DNA pattern in 17 of 28 patients (60.7%) with psoriatic arthropathy but in only 5 of 41 patients (12.2%) with psoriasis alone. Our findings suggest that genes in the immunoglobulin region confer susceptibility to the development of arthropathy in patients with psoriasis.

Adult↗
PubMedDate not supplied

The association of DNA variants at or near the IgH locus with rheumatoid arthritis.

DNA samples from 78 patients with classical or definite rheumatoid arthritis (RA) and 132 healthy controls were analysed by the Southern blotting method, using two DNA probes: the first to the immunoglobulin mu heavy-chain switch region (S mu), in conjunction with the SstI restriction endonuclease, and the second to the D14S1 region, in conjunction with the HindIII restriction endonuclease. The homozygous phenotype for the 6.9 kb S mu fragment was decreased in the patient group (7.8%) compared to controls (19.1%) (P = 0.04). The homozygous phenotype for the 10.3 kb D14S1 fragment was increased in the patient group (38.5%) compared to controls (21.2%) (P = 0.02). The increase was more pronounced in the DR4-positive patients (51.2%) (P versus DR4-positive controls = 0.009). These results suggest that genes on chromosome 14 are involved in the genetics of RA.

Alleles↗
PubMedDate not supplied

An anti-LFA-1 monoclonal antibody (LDA-8) induces cellular aggregation of human lymphoblastoid cell lines and peripheral blood lymphocytes.

The human leukocyte-function-associated antigen-1 (LFA-1) plays a key role in intercellular adhesion interactions of the immune response. A monoclonal antibody (mab), designated LDA-8, is described that recognizes LFA-1. In contrast to nearly all other anti-LFA-1 mabs, which inhibit cellular aggregation, LDA-8 induces cell-cell aggregation. The LDA-8 mab was generated by immunizing mice with membrane fragments from the Jurkat T-cell line. The LDA-8 mab stained peripheral blood mononuclear cells (PBMC), monocyte-depleted peripheral blood lymphocytes, purified monocytes, and a number of T and B tumor cell lines. The LDA-8 mab induced aggregation of PBMC from normal donors, as well as of cells from T-cell lines (MOLT4 and CEM). Control mabs directed against HLA class 1 or CD4 did not induce aggregation. Aggregation was concentration- and time-dependent. EDTA added to the cultures 1 hour prior to or together with the LDA-8 mab did not inhibit LDA-8-induced aggregate formation. Anti LFA-1 alpha-chain mab added to the cells 1 hour prior to LDA-8 mab, or together with the LDA-8 mab, also did not inhibit LDA-8-induced aggregation. In contrast, anti-LFA-1 beta-chain mab, added to the cells together with or 1 hour prior to the LDA-8 mab, significantly inhibited LDA-8-induced aggregate formation. The LDA-8 mab immunoprecipitated two polypeptide chains of 110 kDa and 160 kDa under non-reducing conditions and of 92 kDa and 162 kDa under reducing conditions, from cells of the MOLT-4 or CEM T-cell lines or phytohemagglutinin (PHA)-stimulated PBMC. The molecular mass of these polypeptides was identical to that of polypeptides immunoprecipitated by the anti-LFA-1 TS1.22 mab, suggesting that the LDA-8 mab and the anti-LFA-1 mab recognize the same molecule. This was confirmed by sequential immunoprecipitation. The LDA-8 mab recognizes a unique epitope on LFA-1 and induces cell aggregation that is blocked by mabs recognizing the beta-chain, but not the alpha-chain of the LDA-1 molecule.

Animals↗