SP-A is found principally in the lung, and has been associated with lamella
r bodies also found in the synovial joint. Both SP-A and C1q contain collag
en-like regions, and SP-A and C1q have some structural similarities, both h
aving a globular head region and a collagen-like tail. Here we are able to
show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantib
odies, is present in synovial fluid (SF) isolated from patients with rheuma
toid arthritis (RA); (ii) in absorption experiments only a limited degree o
f cross-reactivity between autoantibodies reactive with C1q and SP-A is obs
erved; (iii) there is no cross-reactivity between autoantibodies reactive w
ith type II collagen (CII) and those reactive with SP-A or C1q; (iv) autoan
tibodies react with polymeric (dimers and larger) SP-A, but not with monome
ric SP-A subunits, indicating that a degree of quaternary structure is requ
ired for antibody binding. Unlike CII, which not accessible in the normal j
oint, both SP-A and C1q are available within the SF in patients with RA and
may therefore provide antigens driving an autoimmune response directed aga
inst collagen-like structures.