Clinical study
Cryoglobulinemia—A clinical and laboratory study: II. Cryoglobulins with rheumatoid factor activity

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Abstract

Detailed clinical and laboratory studies of twelve subjects with cryoglobulins associated with rheumatoid factor activity are presented. These patients constituted 41 per cent of twenty-nine subjects with cryoglobulinemia discussed in the accompanying report.

Eleven of these proteins, ten of which were found in women, were “mixed cryoglobulins” consisting of IgM and IgG molecules. The patients' IgM molecule was essential for cryoprecipitation whereas the IgG could be derived from any source. Two patients had malignant disorders of the plasmacytic and lymphocytic cell series. The other nine had a characteristic clinical picture consisting of pupura, arthralgias and weakness in its early stages, and accompanied by the sudden onset of acute renal failure secondary to diffuse glomerulonephritis in three subjects who progressed to a fatal termination. Although the clinical and pathologic features do not permit definitive classification of this disorder, the condition in these patients appears to fall most closely into the group of “connective tissue disorders,” such as systemic lupus erythematosus. Further support for the existence of immunologic mechanisms is provided by the low serum complement levels in seven of the patients tested, the presence of antinuclear antibodies in four of seven who were studied and the localization of gamma globulin in the glomerular lesions of one patient examined by fluorescence microscopy.

One patient, a young woman with rheumatoid arthritis, had a cryoglobulin composed of polymers of IgG which possessed rheumatoid factor activity. This cryoglobulin, the first IgG rheumatoid factor to be isolated in a high state of purity, may have contributed to the death of the patient by producing marked hyperviscosity.

The possible role of the cryoglobulins in the pathogenesis of the vascular and renal lesions is discussed; the mechanism may be analogous to that seen in experimentally induced serum sickness in rabbits and may involve the localization of rheumatoid factor cryoglobulin complexes in small vessels.

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    This study was supported by U. S. Public Health Service Grants No. AM-1431, 2954, 2489 and AI-01697 and the Arthritis Foundation.

    1

    From the Departments of Pathology and Medicine, and the Rheumatic Diseases Study Group, New York University School of Medicine, and the Medical Group and Division of Social Medicine, Montefiore Hospital, New York, New York.

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