HETEROGENEOUS RF STRUCTURES BETWEEN AND WITHIN HEALTHY-INDIVIDUALS ARE NOT RELATED TO HLA DRB1-ASTERISK-0401

To study variations in Rheumatoid Factor (RF) autoantibodies between a nd within healthy individuals, we have produced and analysed the varia ble heavy chain (V-H) regions of 18 new monoclonal IgM RFs from the pe ripheral blood of two healthy subjects before and after immunization w ith tetanus toroid (TT). The majority of these RFs used germline genes of the V(H)3 family, but RFs of the V(H)1, V(H)2 and V(H)7 families w ere also found. No RF of the V(H)4 RF is found. Fourteen different V, germline (GL) genes encoded the RFs, suggesting an extraordinary heter ogeneity in structure. Consequently, changes in RF V region structures following immunization were difficult to identify. There were, howeve r, structural differences between RFs from the two donors. RFs from on e donor (IP) used more lambda light chains than RFs from the other don or and previously described RFs. In addition, 50% of the RFs from dono r IP were encoded by GL genes frequently found to encode RFs from pati ents with Rheumatoid Arthritis (RA) but not described in RFs from othe r healthy subjects. The predominant use of V(H)3 RFs in the two health y donors contrasts with the over-expression and expansion of V(H)1 RFs in one previously described healthy immunized donor. There are thus l arge individual differences in RF structures, which might be related t o the immunological status, environment or genetic background of the d onors. However, since these three donors are all HLA DRB10401, it is unlikely that this HLA type, associated with seropositive RA, accounts for the individual differences. (C) 1998 Elsevier Science Ltd. All ri ghts reserved.