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To determine the diagnostic value and frequency of tissue deposition of IgG4 in comparison to polyclonal IgG, IgA, IgM, and C3.Oral mucosal biopsies of 82 patients clinically suspected to have mucous membrane pemphigoid (MMP) were analyzed by direct immunofluorescence (IF) using polyclonal anti-human IgG, IgM, IgA, fibrin, complement C3, and anti-human IgG4 subclass monoclonal antibodies.Based on clinical, hematoxylin and eosin (H & E), and direct IF studies, 34 cases were diagnosed as MMP. The most common antibody deposited was IgG (90%), followed by C3 (82%), and IgG4 (71%). In more than half the cases of MMP, IgG4 deposition was seen in combination with IgG and or C3. Strikingly, IgG4 was the sole antibody detected in 2 cases (6%).Our results suggest that the use of monoclonal IgG4 is important in the diagnosis of MMP. We suggest adding monoclonal IgG4 to the routine panel of antibodies used in studies of cases suspected to have MMP to avoid false-negatives.