How are cryoglobulins classified?
Brouet et al published a classification system for cryoglobulinemia in 1974, which is still in use today.
Type I: composed of a single monoclonal Ig, with IgM being the most common. Serum levels of the cryoglobulin are typically very high (5–30 mg/mL, cryocrit >5%), and precipitation occurs rapidly with cooling (usually <24 hours).
Type II: mixed cryoglobulins composed of a monoclonal Ig (typically IgM) that acts as an antibody (e.g., rheumatoid factor [RF]) against polyclonal Ig (typically IgG). Serum levels are usually intermediate (1–10 mg/mL, cryocrit 1%–5%); therefore precipitation may take a few days.
Type III: mixed cryoglobulins similar to Type II, but with polyclonal Ig with RF activity directed against polyclonal Ig. They are usually present in small quantities (0.1–1 mg/mL, cryocrit <1%) and precipitate slowly (up to 7 days); therefore they are more difficult to detect.
Type II to III: an unusual variant composed of oligoclonal IgM and faint polyclonal Igs. It is thought to represent a transition from polyclonal (type III) to monoclonal (type II) mixed cryoglobulinemia (MC) as clonal expansion of B cells progresses
