A Survey of Patients With Elevated Serum IGG4 With Unknown IGG4-related Disease to Whom Biopsy and Performance of Subsequent Specific Staining for Clinical, Laboratory and Pathologic Correlation.

IgG4 is a unique antibody in both structure and function. This molecule accounts for less than 5% of the total IgG in healthy persons and is the least abundant IgG subclass. In contrast to IgG1, IgG2, and IgG3, serum IgG4 concentrations among ostensibly healthy people vary by a factor of more than 100 (normal range, 0.01 to 1.4 mg per milliliter), but IgG4 concentrations within individual persons are generally stable.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome of unknown etiology comprised of a collection of disorders that share specific pathologic, serologic, and clinical features.

These different conditions were previously thought to be unrelated [2-4]. The commonly shared features include tumor-like swelling of involved organs, a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, and variable degrees of fibrosis that has a characteristic "storiform" pattern. In addition, elevated serum concentrations of IgG4 are found in 60 to 70 percent of patients with IgG4-RD.

Two major presentations of this condition, which often affects more than one organ, are type 1 autoimmune pancreatitis (IgG4-related pancreatitis) and salivary gland disease; the later may present as salivary gland enlargement or as sclerosing sialadenitis (formerly termed "Mikulicz disease" and Küttner's tumor, respectively). These conditions often resemble Sjögren's syndrome but are pathophysiologically distinct from this disorder. The preferred name for the overall condition is IgG4-related disease.

The presence of IgG4-bearing plasma cells is required for a diagnosis of IgG4- related disease, but IgG4-positive cells are found in a wide variety of inflammatory infiltrates, and the detection of substantial numbers of IgG4- positive plasma cells is therefore not diagnostic of IgG4-related disease.