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GENDER AND AGE-DEPENDENT ASSOCIATION OF CYTOTOXIC T-LYMPHOCYTE ANTIGEN 4 POLYMORPHISM WITH CORONARY ARTERY LESIONS IN KAWASAKI DISEASE
  1. H C Kuo1,
  2. C L Wang2,
  3. C D Liang3,
  4. H R Yu1,
  5. L Wang1,
  6. I C Lin3,
  7. K D Yang1
  1. 1Division of Pediatric Allergy and Immunology, Department of Pediatrics, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan, ROC
  2. 2Department of Pediatrics, Po-Jen Hospital, Kaohsiung, Taiwan, ROC
  3. 3Division of Pediatric Cardiology, Department of Pediatrics, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan, ROC

Abstract

Objective Kawasaki disease (KD) is a systemic vasculitis of unknown aetiology, but the subsequent development of coronary artery lesions (CAL) remains elusive. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been suggested as a candidate gene for conferring susceptibility to autoimmunity. To this end, the levels of cytokines associated with T helper (Th) 1 and Th2 immunity responses were examined and their association with the disease phenotype and genotype analysed.

Methods CTLA-4 polymorphisms at (−318 C/T) and (+49 A/G) were determined by restriction fragment length polymorphism from 160 KD patients and 563 controls. Plasma samples from a total of 65 KD patients with or without CAL were subjected to measurement of IFN-γ (a Th1 cytokine) and of two cytokines known to be involved in Th2 immunity, including IL-4 and IL-5 by the Luminex-Beadlyte multiplex beadmates system.

Results CTLA-4 polymorphism (+49A) and (−318T) alleles were significantly associated with CAL formation in patients less than 12 months old. In female but not male gender, the (−318T) alleles were significantly related to CAL formation. In further analysis, we found females but not males carrying the CTLA-4 (+49) A allele had significantly lower Th2 cytokines (IL-4 and IL-5) and eosinopohil after intravenous immunoglobulin treatment (p<0.05). The CTLA-4 (−318) T allele had lower albumin levels (p = 0.03) in KD patients less than 12 months old.

Conclusions These results provide evidence supporting the existence of CTLA-4 (+49) A and (−318) T alleles associated with CAL formation in KD patient of female gender and infancy possibly through lower Th2 cytokine and albumin levels.

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