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Biomedical subjects

K I Welsh

Publications and source records attributed to K I Welsh.

At least 235 records · Page 13Linked to original sources
PubMed1983

Immunoglobulin (Gm) allotype frequencies in patients with giant bell arteritis and polymyalgia rheumatica.

Fifty-five Caucasoid patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) were immunoglobulin (Gm) allotyped for this study. Forty-four of these patients had been previously HLA-A,B,C and DR locus allotyped. The incidence of the immunoglobulin allotypic marker Glm(2) was significantly increased in the GCA group (50.00% v. controls 18.75%, P equal less than 0.01). There was a similar but insignificant rise of this Gm marker in the PMR group (27.24% v. 18.75%, NS). The increase in Glm(2) in the GCA group was not accompanied by a corresponding rise in the number of people homozygous for Glm(2), i.e., all the increase could be attributed to patients with the Glm(1,2,3,):G3m(5,10,21)phenotype.

Giant Cell Arteritis↗
PubMed1983

Histocompatibility antigens in psoriasis, psoriatic arthropathy, and ankylosing spondylitis.

Patients with ankylosing spondylitis, psoriatic arthritis, and psoriasis alone were typed for HLA A, B, Cw, and DR antigens, and the antigen frequencies were compared with those in a normal control population and in patients with rheumatoid arthritis. Patients with psoriasis had a significantly raised frequency of Cw6. Those with arthritis in addition to their psoriasis also had raised frequencies of B27 and DR7. Patients with ankylosing spondylitis were characterised by the expected high frequency of HLA B27. Again, those with peripheral arthritis had a higher B27 and DR7 frequency than those without. DR3 is associated with the development of erosions in psoriatic arthritis.

Arthritis↗
PubMed1983

Histocompatibility antigens in polymyalgia rheumatica and giant cell arteritis.

Fifty-five Caucasoid patients with polymyalgia rheumatica or giant cell arteritis were typed for HLA, A, B, C and DR locus antigens. In the total patient group, DR4 had a significantly increased frequency. The prevalence of CW3 and CW6 was also significantly increased, the rise of CW3 possibly being attributable to its well-documented linkage disequilibrium with DR4. The rise in CW6 cannot be attributed to its known linkage disequilibrium with DR7.

Genes, MHC Class II↗
PubMed1982

HLA antigens and Bf allotypes in SLE: evidence for the association being with specific haplotypes.

The clinical features and HLA types of 67 unrelated patients with Systemic Lupus Erythematosus (SLE) were analyzed. The results showed: 1. An increase in frequencies of A1, B8, and DR3. These antigens are in close linkage disequilibrium and our data show that susceptibility to SLE is associated with the presence of all three antigens, implicating the specific haplotype which bears these antigens. 2. An increase in frequency of DR2, but not A3 or B7, these latter two antigens being in linkage disequilibrium with DR2. 3. 73.3% of the 54 Caucasoid SLE group were either B8 and/or DR2. This is in comparison with 37.5% in the controls and the difference is significant (p less than 0.001). 4. There was no association apparent between extent of disease, particular organ involvement and level of circulating antibodies to double stranded DNA with any HLA region product.

Adolescent↗
PubMed1982

The relationship of HLA-B and DR phenotypes to Behcet's syndrome, recurrent oral ulceration and the class of immune complexes.

A series of eighty Caucasian patients was divided into four groups with the mucocutaneous, arthritic, neurological and ocular types of Behcet's syndrome (BS) and a fifth group of patients with recurrent oral ulcers. The immunogenetic basis of the four types of BS was extended from HLA-B locus to the DR locus. Whereas B5 and more precisely the Bw51 split is the most discriminating marker of the ocular type of BS, DR7 also shows a significant increase in the ocular and neurological types. Indeed, most if not all patients with the ocular type have B5 and/or DR7. B12 and/or DR2 is significantly increased at the less severe end of the spectrum, the mucocutaneous and arthritic types. Patients with recurrent oral ulcers also show an increase in B12 and/or DR2. However, B12 and/or DR7 shows an increase in the relative risk in all four types of BS. These results suggest that HLA-B12, B5, DR7 and DR2 might in some way be associated with tissue localization of disease. Alternatively, since patients with HLA-B12 show a significantly greater ratio of IgG:IgA circulating immune complexes than those with B5/DR7/DR2, tissue localization might be influenced by the immune complex isotype. A significant relationship was also found between the MT2 and MT3 B cell alloantigen system and BS, with particular reference to MT2 and the neurological type and MT3 and the ocular type of BS.

Antigen-Antibody Complex↗
PubMed1981

Immunogenicity of human amniotic epithelial cells after transplantation into volunteers.

Human amniotic epithelial cells do not express on their surfaces HLA-A, B, C, and DR antigens, or beta 2-microglobulin. In vitro these cells synthesise the enzymes lacking in patients with selected enzymatic deficiencies: the survival of a transplanted monolayer of human amniotic epithelial cells was therefore investigated in seven volunteers. None of the volunteers showed clinical signs of acute rejection, and amniotic epithelial cells were demonstrated by biopsy up to 7 weeks after implantation. HLA antibodies were not detected in samples of serum from four volunteers thoroughly investigated, and there was no in-vitro lymphocyte reaction to the amniotic cells in two of them. The results suggest that acute immune rejection does not occur after the transplantation of human amniotic epithelial cells.

Adult↗
PubMed1981

Do alleles in linkage disequilibrium compensate for each other's disadvantageous effects?

When alleles from two different loci behave as independent factors it is possible to calculate the expected frequency of their joint occurrence. In the HLA system significant departures from expected haplotype frequencies occur. Thus antigen B8 occurs together with A1 or/and DR3 in about 95 cases out of 100 (the figure expected by chance is about 45 out of 100). In a similar manner the antigens A3, B7 and DR2 are found associated very much more often than expected by chance alone. The reasons for these observations are obscure, but Fischer (1930) and more recently Bodmer (Bodmer & Bodmer 1978) have argued that some form of natural selection is a major factor in the occurrence and maintenance of linkage disequilibrium. In the present study we show that individual alleles of the common haplotype A1-B8-DR3 can exert different effects as regards IgE levels. This may provide evidence that one of the contributory mechanisms leading to linkage disequilibrium involves selection against individuals having a harmful allele unless it is in association with another conferring compensatory effects.

Alleles↗
PubMed1980

HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis.

To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3. The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications. Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.

Adult↗
PubMed1980

Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility.

26 patients with systemic lupus erythematosus (SLE) induced by treatment with the antihypertensive drug hydralazine were investigated to determine if predisposition to the toxic effect was associated with an HLA-DR antigen. 25 of the 26 patients were slow acetylators. The group was compared with three others (1) 113 healthy subjects, untested for acetylator phenotype, (2) 16 slow-acetylator hypertensive patients treated with hydralazine for more than a year without developing SLE, and (3) 20 patients with idiopathic SLE. The frequency of HLA-DR4 (73%) was significantly higher in the group with hydralazine-induced SLE than in the other groups (respectively 33%, 25%, and 25%). The ratio of women to men affected was 4:1. If the slow acetylators treated with hydralazine were analysed as one group, it was observed that all women with DR4 developed hydralazine-induced SLE; the only men to do so were those with DR2 who were receiving 200 mg hydralazine per day. These observations have led us to suggest guide lines for hydralazine therapy and point to a striking association between an HLA-DR antigen and an adverse reaction to a therapeutic agent. It was also noted that the distribution of DR antigens in the hydralazine-SLE patients was significantly different from that in the group with idiopathic SLE. This supports the view that the syndromes are separate entities.

Acetylation↗
PubMed1979

Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. I. Retransplantation of (AS X AUG)F1 kidneys into secondary AS recipients.

Long survival of (AS X AUG)F1 rat kidney allografts in AS recipients was induced by passive enhancement with AS anti-AUG antiserum at the time of grafting. After 1-3 mo, the kidney allografts were transferred to second AS recipients, either naive or sensitized against AUG tissue. Naive second recipients did not reject the grafts acutely and failed to mount T-dependent immunity against AUG targets. When later challenged with spleen cells carrying the AUG haplotype, the naive second AS recipients showed strong IgM, IgG, and cytotoxic T-cell responses after grafting, and the kidneys were rapidly destroyed by immune rejection in all but one rat. It is concluded that long-surviving kidney allografts fail to activate helper T cells and induce in naive second recipients the same state of unresponsiveness observed in the first recipient.

Animals↗
PubMed1979

Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. II. Retransplantation of (AS X AUG)F1 kidneys from AS primary recipients into (AS X WF)F1 secondary hosts.

Long surviving, passively enhanced (AS X AUG)F1 kidneys carried by AS recipients were retransplanted into (AS X WF)F1 second hosts. Acute graft rejection did not occur. Only one of six secondary recipients mounted a significant T-dependent IgG lymphocytotoxic antibody response. In all six, generation of cytotoxic T cells was markedly slower and depressed. These results are compatible with the hypothesis that kidney parenchyma, although carrying major histocompatibility complex specificity is able to induce T-independent but not T-dependent alloimmunity. A corollary is that passenger cells are responsible for exciting the T-dependent allimmune response normally observed after grafing. The practical difficulty of eliminating all T-dependent immunogenicity from (AS X AUG)F1 kidneys was emphasized by the observation that a 3-d residence in an intermediate AS recipient was insufficient time to prevent acute graft rejection after retransplantation.

Animals↗
PubMed1977

The immune response to allogeneic rat platelets; Ag-B antigens in matrix form lacking Ia.

Allogeneic rat platelets fail to induce either primary antibody or cell-mediated immune responses despite repeated injections. Platelets bear Ag-B epitopes which are capable of being recognized by antigen-reactive T and B cells since primed rats develop secondary responses after challenge with allogeneic platelets. The secondary responses induced decrease rather than increase on repeated injection of platelets. Repeated injection of allogeneic platelets into nonprimed rats leads to a state of specific, partial non-reactivity; recipients given such treatment show marked depression of cytotoxic antibody responses, but normal cellular immunity after challenge with viable lymphoid cells taken from the platelet-donor strain. Injection of normal rats with allogeneic platelets mixed with 3rd party, viable lymphoid cells, does not provoke an anti-platelet Ag-B antibody response.

Animals↗
PubMed1977

Quantitation of beta2-microglobulin and HLA on the surface of human cells. I. T and B lymphocytes and lymphoblasts.

Relative amounts of beta2-microglobulin (beta2m) and of HLA specificities were analysed on the surface of resting unfractionated peripheral human lymphocytes, enriched B and T cells, and on in-vivo- and in-vitro-stimulated lymphoblasts. Single-cell cytofluorometry and a very sensitive radioimmunoassay were used to determine as closely as possible the absolute amounts of membrane-bound beta2m/HLA antigens. B and T "resting" and "stimulated" lymphoid cells express very similar numbers of beta2m and HLA antigenic determinants, respectively, per unit of surface area when compared with each group, although beta2m was found to exist in two- to three-fold excess of HLA.

Antibodies, Anti-Idiotypic↗
PubMed1977

Quantitation of beta2-microglobulin and HLA on the surface of human cells. II. In vitro cell lines and their hybrids.

Beta2-microglobulin (beta2m) participates as an integral part in molecules of the major histocompatibility complex (MHC) type. Absence of beta2m makes the residual heavy MHC chain largely inactive as antigen. Striking reductions in the density per unit surface area of beta2m in seven out of nine malignant lymphoid tumour lines in comparison with normal lymphocytes or "immortalized" Epstein-Barr-virus-transformed lymphoblastoid lines were found is this study. This would seemingly represent a specific reduction in the ability of the malignant cells to express actively produced beta2m, since their HLA antigenic determinants were not reduced to the same extent and no indications were obtained suggesting that free beta2m could transfer from one cell to another. However, that beta2m is important in conveying serological specificities of MHC type to cells was shown by fusion of beta2m-negative and beta2m-positive cells, yielding hybrid cells with synergistically increased numbers of detectable, HLA-related determinants. Whether the reduction of beta2m on malignant versus nonmalignant lymphoid cells bears any relevance as to emergence of the malignant clones and resistance to possible anti-tumour reactions would now be an issue for study.

B-Lymphocytes↗