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Immunogenetics of familial rheumatoid arthritis: a study of 41 multicase families.

HLA haplotypes were studied in 41 unrelated families from North India with multiple cases of rheumatoid arthritis. Affected sibpairs shared parental HLA haplotypes more often than expected (chi 2 = 13.6) according to Mendelian segregation. Using the method of sibpair ratio, nonrandom segregation of parental haplotypes was observed among affected sibs. HLA-DR4 was observed in 70% of the probands while among DR4 negative probands, DR10 occurred more frequently. However no specific haplotypic association with the disease was observed in these families.

Adult↗

[Diabetes mellitus in the elderly: a study on its clinical presentation, C-peptide reserve, and immunogenetic markers of insulin dependence].

In order to evaluate clinical presentation and to determinate classification criteria of type 1 diabetes in the elderly, we carried out a study in 258 diabetic patients more than 60 years old of which 100 used insulin by failure to oral hypoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheral vascular disease 34% and stroke 30%. Non-proliferative retinopathy 47%, nephropathy 16% and peripheral neuropathy 37%. Cardiovascular risk factors as obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Post-glucagon C-Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 11 diet and 40 OHA. Older patients on treatment with insulin had longer duration of disease, less obesity, low level basal of C-Peptide and a low response to post glucagon C-Peptide (0.94 +/- 0.5 pmol/ml) compared with patients on diet (1.8 +/- 0.9 pmol/ml) and OHA (1.8 +/- 0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%) than other older diabetics. The ICA was negative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying type 1 (insulin-dependent) diabetes is the measurement of basal and post-glucagon C-Peptide. HLA-DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management.

Aged↗

Quality control in immunophenotyping: U.S. efforts to establish common methodology and their impact. American Society for Histocompatibility and Immunogenetics.

Several organizations in the United States have recently been involved in the quality assurance of immunophenotyping using flow cytometry. These activities include publication of guidelines for immunophenotyping, particularly in human immunodeficiency virus infection, performance evaluation and proficiency testing programs, and training and continuing education programs. Through questionnaires and results from performance evaluation programs, variability in test results has been decreasing the last few years, and more laboratories are beginning to use the same specimen processing and data analysis procedures.

Flow Cytometry↗

Prevalence of antikeratin antibodies in Greek patients with rheumatoid arthritis. A clinical, serologic, and immunogenetic study.

OBJECTIVE: The presence of antikeratin antibodies (AKA) has been associated with rheumatoid arthritis (RA) in patients from north and central Europe. Our aim was to investigate the prevalence of AKA in Greek patients with RA. METHODS: One hundred and twenty two sera of Greek patients with RA were tested for the presence of AKA by an indirect immunofluorescence technique, and HLA-DR typing was performed by restriction fragment length polymorphism. RESULTS: Nineteen of 122 (16%) Greek patients with RA were positive for AKA. The percentage of AKA in Greek patients with RA is lower than described previously. These antibodies correlated with a male preponderance (p < 0.01) and were associated with the presence of rheumatoid factor (RF) (p < 0.05) and with HLA-DR1 antigen (p < 0.05). CONCLUSION: Our results suggest that AKA are present frequently in Greek patients with RA. Their presence was found to be associated with RF and HLA-DR1 antigen. This emphasizes the different clinical expression of RA in Greece.

Adult↗

Phage display cloning and characterization of an immunogenetic marker (perinuclear anti-neutrophil cytoplasmic antibody) in ulcerative colitis.

Ulcerative colitis (UC) is genetically associated with a marker serum Ab (pANCA), identified by its reactivity with a neutrophil Ag. This study utilized phage display technology to clone and characterize pANCA, which has resisted conventional isolation strategies. Since spontaneous pANCA-secreting B cells are detectable in UC lamina propria lymphocytes, this cell source was used to construct a complete IgG1-kappa Ig library. Selection of phage by panning with fixed neutrophils yielded a 195-fold enrichment after five cycles of panning. BstN1 fingerprinting of the enriched library revealed two predominant clones, and DNA sequencing demonstrated highly homologous heavy and light chain variable region segments. Clones were reengineered to express soluble Fab, and neutrophil binding was verified by ELISA. Detailed studies with the two recombinant Fabs, NANUC-1 and -2, validated their identity with serum pANCAs by the criteria of immunofluorescence, confocal microscopy, and DNase I sensitivity. NANUC-1 and -2, like serum UC-pANCA, lack reactivity with previously characterized ANCA-reactive neutrophil proteins and thus detect a novel Ag(s). This study demonstrates the feasibility of selecting phage display Ab libraries on uncharacterized biologic substrates to isolate marker Abs of pathogenic importance.

Amino Acid Sequence↗

Immunogenetic control of brain tumor growth in rats.

The susceptibility to intracerebral and s.c. growth of a transplantable gliosarcoma in genetically inbred rats correlated with histocompatibility type. The genetic control of tumor growth was tested in a cross between a tumor-susceptible strain (F344, Ag-B1) and a tumor-resistant strain (YO, Ag-B2). Susceptibility was transmitted as a dominant trait, and at least two genes or gene complexes were involved: one was linked to the major histocompatibility complex and one segregated independently of it. The genetic mechanisms did not appear to be affected significantly by the site (environment) in which the tumor grew. Antibodies to Ag-B1 histocompatibility antigens, which were those of the strain in which the tumor originated (F344), and to tumor-associated antigens were generally present in animals in which the tumor had regressed. Only tumor-specific antibodies appeared in the sera of Ag-B1 animals that had the tumor. A cytotoxic lymphokine was present in the sera of tumor-bearing animals, but its level did not correlate with tumor growth or regression.

Animals↗

Immunogenetic studies of Behçet's disease.

Behçet's disease has been shown to be strongly associated with the human leukocyte antigen (HLA) B51, not only in the Japanese but also in many other ethnic groups living in the area that extends from the Middle East to Japan. Specific antigen presentation by B51 molecules may be involved in the development of Behçet's disease. Furthermore, studies of the HLA-C genotype conducted using a polymerase chain reaction-sequence specific primers method have suggested that the gene involved in the pathogenesis of Behçet's disease is not the HLA-C gene but some other gene located near the HLA-B gene. Polymorphic analysis of the Tau-a microsatellite located between the HLA-B and TNF genes have also indicated that the Behçet's disease gene is located near the HLA-B gene but is not the HLA-B51 gene itself. We and others believe that many important genes exist in the region located between the TNF and HLA-B or HLA-C genes, including the MIC, PERB, and NOB genes. In this paper, we review current data on genetic factors involved in the development of Behçet's disease.

Behcet Syndrome↗

Immunogenetic risk factors of dilated cardiomyopathy.

This work deals with the investigation of the HLA system antigen, classes A, B, CW and DR, in 100 patients with dilated cardiomyopathy and 200 healthy donors. It was shown that the HLA system antigen is involved in the hereditary predisposition to dilated cardiomyopathy and in its clinical polymorphism determination. The HLA system antigen distribution in patients with dilated cardiomyopathy clearly differs from the same index in the general population following this medical examination. The direct connection between the dilated cardiomyopathy and the HLA DQA1 gene confirms the hypothesis on the genetic determinism of this disease.

Adult↗

Immunogenetic and microbial factors in acute anterior uveitis.

OBJECTIVE: To characterize the rheumatic diseases associated with acute anterior uveitis and examine the potential role of Yersinia enterocolitica in the pathogenesis of acute anterior uveitis. METHODS: 44 patients with acute anterior uveitis were assessed for evidence of an underlying rheumatic syndrome by history and examination. HLA profiles were identified by serologic and molecular techniques. Serological analysis of patients' sera for the presence of antibodies to Y. enterocolitica was by Western blot. RESULTS: 30 of the 44 patients had musculoskeletal symptoms. Of these, 8 had ankylosing spondylitis, 4 reactive arthritis, 2 undifferentiated spondyloarthropathy (SpA), 2 inflammatory bowel disease, one seronegative polyarthritis, and 13 mechanical back pain. Of 42 patients typed, 29 (69%) were HLA B27 positive and an additional 7 patients expressed a crossreactive group antigen (86% of total group B27 or CREG positive). Western blot analysis of the sera revealed increased frequency of antibodies to Yersinia compared with a control population. Antibodies directed against the 36 and 27 kDa Yersinia antigens were recognized with greater frequency (p < 0.05) in patients with acute anterior uveitis than in controls. IgG reactivity was more pronounced than IgA reactivity. Adsorption studies showed significant cross reactivity of anti-Yersinia antibodies with Salmonella typhimurium. Among the patients with acute anterior uveitis anti-Yersinia reactivity did not correlate with the HLA profile, nor with the presence of an underlying rheumatic disease. CONCLUSION: SpA represent the commonest underlying rheumatic disorders associated with acute anterior uveitis. The majority of patients with acute anterior uveitis possess HLA-B27 regardless of whether there is underlying SpA. Patients with acute anterior uveitis show increased frequency of anti-Yersinia antibodies compared with controls. Many of these antibodies appear to be directed against antigenic determinants shared among gram negative bacteria and thus cannot constitute definitive evidence for a causal role specifically for Yersinia in acute anterior uveitis. Acute anterior uveitis represents an interplay of host susceptibility and microbial triggers, as is the case for the SpA in general.

Acute Disease↗

[Immunogenetic mechanisms in autoimmune processes: disorders of immune regulatory mechanisms, genetic determination of autoimmunity, effector mechanisms of autoimmune processes and their therapy].

Autoimmune disease represent a great social and medical problem. 5 to 7% of population suffer from these chronic debilitating disorders. Our knowledge about the immune system and the genetic determination of its components and processes has considerably increased in the fast few years. The purpose of the two articles on autoimmunity published in the previous and this issue is to offer a reader a topical status of the development in this field. Autoantigens, their presentation to T lymphocytes and superantigens were discussed in the first article. The breakdown of regulatory mechanisms of immunity, the genetic basis of autoimmunity, the effector mechanisms responsible for tissue damages and their therapy are reviewed in the presented article. (Tab. 4, Fig. 1.).

Autoimmune Diseases↗