A family containing two apparently healthy brothers with profound early complement component depletion (Cl, C4, C2) and mixed IgG-IgM polyclonal cryoglobulIns was studied. The ctyoglobulins possessed rheumatoid factor activity and depleted early complement components in normal human serum. plement system. These deficiency states, both hereditary and acquired, are often associated with autoimmune diseases, most notably systemic lupus erythematosus (SLE) or a lupus-like syndrome (1). Cold precipitable proteins or cryoglobulins, presumably reflecting immune complex phenomena, have been found in many patients with hypocomplementemia (2). Cryoglobulins have also been associated with a variety of infectious, lymphoproliferative, and autoimmune diseases (3). An "essential" form of cryoglobulinemia, first described by Meltzer and Franklin (4,5), has also been described where the cryoglobulins are typically mixed IgG-IgM complexes which demonstrate rheumatoid factor activity and deplete early complement components (6). Clinical symptoms usually occur in this setting and include arthralgias, purpura, weakness and, frequently, glomerulonephritis (4,5).The present report describes the first cases of two apparently healthy members of the same family with profound early complement component deficiency and mixed cryoglobulinemia.
MATERIALS AND METHODSIndex case report. The proband, a 36-year-old white man, was referred for evaluation of possible rheumatoid arthritis. Twelve years earlier he had abrupt onset of polyarthritis affecting small joints of the hands, wrists, elbows, shoulders, hips, knees, and ankles. During that evaluation a rheumatoid factor test was positive, and the diagnosis of rheumatoid arthritis was made. However, his articular syndrome resolved after 3 4 weeks, and he remained well for the next 12 years, except for occasional hrthralgias and the development of a mechanical low back syddrome. It was because of this axial skeletal complaint coupled with the presence of a persistently positive rheumatoid factor test and hypocomplementemia that he was referred. He denied any constitutional