Rheumatoid arthritis in Greece: clinical, serological and genetic considerations

In the present study we summarize the clinical, serological and genetic peculiarities of Greek rheumatoid patients. Initially we demonstrated that Greek RA patients have a high frequency of Ro(SSA) antibodies in their sera and that these patients present a high incidence of D-penicillamine (DP) side effects. In addition, we showed that these patients were predominantly female and had an increased incidence of positive salivary gland biopsy, compatible with Sjögren's syndrome (SS). Subsequently, longitudinal studies showed that this subgroup of Ro(SSA) positive RA patients present erosive arthritis in a similar frequency compared to Ro(SSA) negative patients. In addition, we evaluated the prevalence of secondary SS in RA patients. We found that secondary SS was common (31%), benign, subclinical and required specific tests for its diagnosis. To answer the question regarding the existence of additional markers of DP toxicity (other than Ro(SSA) antibodies) in RA patients, we found that in addition to Ro(SSA) antibodies, circulating cryoglobulins were associated with DP side effects. All of these observations prompted us to compare the clinical, serological and radiological expression of RA in Greek and British patients. We found that Greek patients had less inflammatory articular disease, fewer extra-articular manifestations, less radiological joint destruction, and a high frequency of Ro(SSA) antibodies linked to a higher prevalence of secondary SS. Furthermore, a study from our group showed a lack of association of RA with HLA antigens, and only a weak association with HLA-DR1 and DR4 antigens. To clarify the clinical, serological and genetic differences between RA in Greece and that in other European countries, we examined HLA class II DNA polymorphisms in 92 adult Greek RA patients and compared them with those of 84 healthy ethically matched controlled individuals. We showed that RA in Greece is associated with the same HLA-DR beta alleles which confer susceptibility in northern European caucasoids. However, whereas 83% of northern European patients carry the HLA-DR beta motif, this was found in 43.5% of Greek patients. In addition, we investigated whether HLA-DR4 is a marker of disease severity in Greek RA patients. There was no difference between the DR4+ and DR4- patients with respect to disease duration, severity of arthritis, and the functional and anatomical joint scores. There was no statistical difference in the clinical manifestations among patients with different HLA-DR4 subtypes. The same was also true when the clinical picture was correlated with the "shared RA epitope". Finally, we investigated the prevalence of antikeratin antibodies (AKA) in our RA population. 16% of the patients had positive AKA antibodies. These antibodies were correlated with the presence of RF and HLA-DR1 antigen. We conclude that RA in Greece differs on clinical, serological and genetic grounds compared to RA in northern European countries. Multicenter European studies may provide valuable information regarding the differences observed among Greek and northern European RA.