Complex associations between HLA-DRB1 genes and female rheumatoid arthritis - Results from a prospective study

We followed 138 Spanish patients (37 men and 101 women) with rheumatoid art hritis (RA) co analyze whether patient sex influenced the HLA-DRB1 associat ions with disease susceptibility. Results showed that, although a high incr ease of che shared epitope (SE) was observed in both Senders, distribution of HLA-DRB1 specificities differs from males to females: DR1 was increased among male patients, whereas DR4 as well as DR10 were preferentially associ ated with female RA. To further explore whether this phenomenon operates ei ther on susceptibility or on disease progression, 82 patients (25 males and 57 females) among the whole group were followed during the first 8 to 10 y ears of their disease. Results from this prospective study showed that the association of the SE with radiological disease severity was found in both male and female patients, although it was stronger among the latter group. Interestingly, DR1- as well as DR4-related alleles contributed to the high frequency of SE among female patients with early small-joints severe RA and /or long-term large-joint: erosions. These results suggest that: HLA polymo rphism might be involved in RA pathogenesis through two mechanisms: (a) in combination with patient sex, operating in disease induction; and (b) indep endent of patient sex, influencing disease severity and progression. (C) Am erican Society for Histocompatibility and Immunogenetics, 1999. Published b y Elsevier Science Inc.