Three patients with cutaneous vasculitis and one patient with digital gangrene had a negative or equivocal test for cryoglobulins but a positive result in a modified assay for cryoproteins ( hypocryoglobulins [ HGs ]) in which serum is rendered hypotonic by dilution with an equal volume of distilled water before incubation in the cold. Each cryoprecipitate contained a mixture of immunoglobulins, and in two instances, a monoclonal component was demonstrated. Rheumatoid factor activity was found in two precipitates. All four patients improved with plasmapheresis, and two subsequently responded to alkylating agents. Seven patients with conventional cryoglobulins had precipitation from diluted serum as well, but none had a substantial increase in precipitation in the HG assay. Only two of five patients with seropositive rheumatoid arthritis had abnormal levels of HG. Hypocryoglobulins are a new category of abnormally insoluble serum proteins, probably closely related to conventional cryoglobulins, which are readily detected in a simple precipitation assay.

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