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Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers
Insights
This study identifies two distinct Graves' disease patient groups using genetic markers and clinical features. One group shows severe disease with ophthalmopathy, while the other has milder symptoms, aiding personalized treatment strategies.
Area of Science:
- Immunogenetics
- Endocrinology
- Clinical Medicine
Background:
- Previous cluster analysis identified Graves' disease subsets based on clinical and HLA-A/B data.
- HLA-B8 prevalence was higher in the severe, recurring disease subset with ophthalmopathy.
Purpose of the Study:
- To investigate if HLA-A, HLA-B, HLA-C, DR antigens, and IgG heavy chain markers can segregate new Graves' disease patients into clinically relevant subsets.
- To validate and expand upon previous findings regarding genetic and clinical associations in Graves' disease.
Main Methods:
- Cluster analysis of 117 new Graves' disease patients.
- HLA typing (HLA-A, B, C, DR) and IgG heavy chain marker analysis.
- Correlation of genetic markers with clinical features like ophthalmopathy, recurrence, antibody titres, and family history.
Main Results:
- Two patient clusters (C1 and C2) were identified.
- Cluster 1 (severe): High incidence of exophthalmos, hyperthyroidism recurrence, high anti-thyroglobulin antibodies, associated autoimmune diseases, familial tendency, and larger goitres. Associated with HLA-B8 and HLA-DR3.
- Cluster 2 (mild): Associated with HLA-B12 and HLA-DR2.
Conclusions:
- Genetic markers like HLA-B8, HLA-DR3, HLA-B12, and HLA-DR2, along with clinical features, can effectively segregate Graves' disease patients into distinct severe and mild subsets.
- These findings support the potential for personalized medicine approaches in managing Graves' disease based on identified patient clusters.
Abstract:
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)
