JCEM-jc-2018-01974-KAHALY-SUPPLEMENTAL-TABLES.pdf

Context: The
Major Histocompatibility Complex (MHC) strongly contributes to the development
of polyglandular autoimmunity (PGA).

Objective:
To evaluate the impact of gender on human leukocyte antigen (HLA) association
with PGA for the first time.

Design: Cross-sectional
immunogenetic study

Setting:
Academic, tertiary referral, orphan disease center for PGA (ORPHA 282196) and immunogenetics
laboratory

Subjects: 158
patients with coexistent type 1 diabetes and autoimmune thyroid disease (adult
type three PGA, ORPHA 227982) and 479 unrelated healthy controls

Methods:
All 637 subjects were typed for HLA-A, -B, DRB1, -DQA1, and –DQB1
alleles at a two-field level.

Main
outcome measure: Modification of the gene-disease association by
gender

Results: MHC
class I HLA-A association was
gender-related to both the total adult type three PGA collective (n=158, p=0.0065) as well as in PGA patients
with autoimmune Hashimoto’s thyroiditis (n=91, p=0.010). Compared to HLA-A*02:01, A*11:01 was overrepresented in male patients, yet underrepresented
in females (OR 1.49, 95% CI 0.55-3.88 vs. 0.42, 0.12-1.17). A*24:02 was underrepresented in males but
not in female patients (OR 0.37, 95% CI 0.111.04 vs. 1.19, 0.65-2.15). Excluding
the five most frequent alleles (A*01:01, A*02:01, A*03:01, A*11:01, and
A*24:02), the sum of all other identified alleles was underrepresented in male
patients (OR 0.37, 0.18-0.72, p=0.0046).
The strong MHC HLA-B association with PGA (p<0.0001)
was not gender-related (p=0.55). Further,
no interaction with gender was observed for the MHC class II HLA-DRB1, DQA1, and DQB1 alleles.

Conclusion: MHC
class I HLA-A association with type
three PGA is significantly affected by gender.