Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers.
In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than among controls (chi2 = 4.71, p less than 0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patient clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster.(ABSTRACT TRUNCATED AT 250 WORDS)
Frecker
M F
MF
Preus
M
M
Kozma
L
L
Krasrits
E
E
Stenszky
V
V
Balazś
C
C
Farid
N R
NR
D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006111:Graves Disease / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D015235:HLA-B Antigens; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male
D005819:Genetic Markers; D006680:HLA Antigens; D015235:HLA-B Antigens; C035015:HLA-B12 antigen; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains