The risk for rheumatoid arthritis (RA) is associated with human leukocyte antigen (HLA)-DRB1*04 non-inherited maternal HLA alleles (NIMA) in younger-onset female patients but not in older-onset male or female patients, study findings indicate.
“Some patients with RA lack RA-associated HLA alleles,” note Katherine Guthrie (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA) and colleagues.
They add that previous studies, with conflicting results, have investigated whether exposure to NIMA might explain RA in these individuals.
In this study, Guthrie and team examined NIMA in 620 patients from 306 families taking part in the North American Rheumatoid Arthritis Consortium. There were 176 patients without HLA-DRB1*04 and 86 without the HLA shared epitope (SE).
The researchers compared the frequency of NIMA encoding HLA-DR4 or the SE to the non-inherited paternal allele (NIPA). Among HLA-DRB1*04-negative patients with RA, they found a non-significant increase of HLA-DRB1*04-positive NIMA compared to NIPA (27% vs 20%).
The analysis was then stratified by gender and age of onset “because parity has been reported to modulate RA risk,” the researchers explain.
Interestingly, women with RA onset during their reproductive years (younger than 45 years) showed an increased prevalence of DRB1*04-positive NIMA compared to NIPA, whereas women older at onset showed a decreased prevalence of DRB1*04-positive NIMA compared to NIPA.
“These observations could help explain conflicting prior results of NIMA in RA,” reason Guthrie et al in the Annals of the Rheumatic Diseases.
Among male patients the prevalence of HLA-DRB1*04-positive NIMA did not vary from NIPA. In addition there was no difference between SE-positive NIMA and NIPA in men or women.
The researchers conclude: “Our observations indicate further investigation of NIMA is needed among women with RA for whom pregnancy history is known, as well as the HLA genotypes of children born prior to RA onset.”