Pathogenic role of a monoclonal IgA (?) anti-IgG paraprotein associated with hemorrhagic diathesis, rheumatoid arthritis, vascular purpura, and acute membranoproliferative glomerulonephritis

Abstract

Sixteen years earlier a 42-year-old woman with an IgA kappa plasma cell neoplasm presented with bleeding disorder. Her prolonged course was complicated by subsequent development of rheumatoid arthritis, vascular purpura, and an acute membranoproliferative glomerulonephritis (MPGN). The paraprotein and its (Fab')2 fragment showed affinity for a test myeloma IgG2 (lambda ) paraprotein. The patient's serum and the IgA-IgG complex separated by gel filtration did not exhibit cryoprecipitation. The complex also did not dissociate by ultracentrifugation. Electron microscopic and immunofluorescent studies of a renal biopsy sample taken during the episode of nephritis showed subendothelial deposits and a lacy fluorescent pattern strongly positive for IgA and IgG. The same immunoglobulins were eluted from the kidney at postmortem. A low concentration of monoclonal IgA kappa (antibody) and excess unbound polyclonal IgG (antigen) were demonstrated in the patient's serum at the time of MPGN, apparently analogous to the conditions necessary for the induction of experimental immune complex nephritis.

Selective bone marrow involvement of lymphoplasmacytic cells secreting monoclonal IgA rheumatoid factor in a patient with Sjögren's syndrome and serum hyperviscosity.

“…A similar case of SS with monoclonal IgA with rheumatoid activity and hyperviscosity syndrome has been described by Sugai et al7 It has been shown that the formation of monoclonal immunoglobulin-polyclonal IgG immune complexes with 'intermediate' coefficient sedimentation (13-14 S) can be responsible for serum hyperviscosity. [17][18][19] In this case gel filtration studies of whole serum showed that the major portion of the immune complexes had a molecular weight of 680 kilodaltons. We also confirmed that the immune complexes were composed of monoclonal IgAx rheumatoid factor bound to polyclonal IgG.…”