Immunogenetic association and thyroid autoantibodies in juvenile autoimmune thyroiditis in North India.
OBJECTIVE
Autoimmune thyroid diseases (AITD) encompass a number of conditions that have in common cellular and humoral responses targeting the thyroid gland. Interactions between susceptibility genes and environmental triggers are thought to initiate an autoimmune response to thyroid antigens leading to disease manifestation. Commencement of the disease in childhood leads to the presumption that genetics may have an important role in the causation of the disease.


METHODS
The present study was aimed at evaluating the human leucocyte antigen (HLA) encoded susceptibility to develop juvenile autoimmune thyroiditis (JAT) in patients from North India.


METHODS
We studied 48 consecutive patients of JAT along with 176 first-degree relatives for their thyroid function (FT4, TSH) and anti-thyroid peroxidase antibody status (AbTPO).


METHODS
HLA studies were carried out using serology for HLA-class I antigens and DNA analysis of HLA-class II alleles. The data were compared with a cohort of 308 ethnically matched healthy individuals.


RESULTS
We observed overt hypothyroidism in 50% and AbTPO positivity in 70.8% of the index cases. Among the first-degree relatives, goitre was observed in 51.7%, thyroid dysfunction in 28.4% and AbTPO in 29.5% of individuals. Of the 37 relatives who underwent fine-needle aspiration cytology (FNAC), 60% had evidence of chronic lymphocytic thyroiditis (CLT). A strong positive association of HLA-DRB1*1404 was observed with the JAT (35.4%vs. 10.4%, chi2 = 19.8, Pc = 0.0001). We also observed a higher (72%, P = 0.03) paternal transmission of HLA-DRB1*1404 to affected offspring in comparison to unaffected offspring. HLA-DRB1*03 was also increased among JAT patients but did not reach statistical significance.


CONCLUSIONS
These studies point towards an important role of immune modifying genes, such as HLA, in influencing susceptibility to juvenile-onset AITD.
Kanga
U
U
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Tandon
N
N
Marwaha
R K
RK
Khanna
R
R
Bhattacharya
B
B
Singh
S
S
Kumar
N
N
Mehra
N K
NK
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007125:Immunogenetics; D007194:India; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology*
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D007453:Iodide Peroxidase