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Detection of immunoreactants including IgG, IgM, IgA, and C3 by direct immunofluorescence (DIF) from skin is useful for distinguishing lupus lesions from other skin disorders. Despite their diagnostic value, the type and number of cutaneous immunoreactants as they relate to serological disorders and disease severity has been poorly studied. We examined 36 patients with systemic lupus erythematosis (SLE) with positive DIF (DIF+) and 28 patients with negative DIF (DIF-) tests performed on lesional skin. Among DIF+ patients, the most frequent patterns of immunoreactants were IgM alone (36%) and the coexistence of IgM with C3 (28%). IgM was the highest detected individual immunoreactant (86%). As classified by number, 17 of 36 DIF+ patients had one immunoreactant (= 1), while the remaining patients had two to four immunoreactants (>1). Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI). The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI. These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant. Collectively, the presence of multiple immunoreactants in lesional skin implies a more severe disease activity of SLE, while a single immunoreactant may be equal to the absence of immunoreactants (DIF-) in terms of predicting disease activity.