The immunopathology of herpes gestationis. Immunofluorescence studies and characterization of "HG factor".

Nine skin biopsies from seven herpes gestationis patients were studied by immunofluorescence (IF) techniques. Basement membrane zone (BMZ) deposition of C3 and properdin was present in all nine skin specimens, while IgG deposition was apparent in only one. With in vitro C3 IF staining, positive BMZ staining (HG factor activity) was noted with all seven of our patients' serum samples tested. By standard indirect IF staining, however, only one of these serum samples contained BMZ antibodies of the IgG type. Two cord serum samples, tested by these same methods, yielded positive in vitro C3 staining (HG factor activity) but negative indirect IF staining (IgG). HG factor activity was found to be stable at 56 degrees C for 30 min and in two of three specimens at 56 degrees C for 1 h. Treatment of the complement source (normal human serum) used in the in vitro C3 staining assay with Mg2-EGTA or use of C2-deficient serum as the complement source inhibited HG factor activity. HG factor blocked the specific staining of the BMZ of normal human skin by labeled bullous pemphigoid antibodies. By sucrose density gradient ultracentrifugation and gel chromatography (Sephadex G-200), HG factor activity eluted with IgG-containing fractions. The highly purified IgG fraction of two herpes gestationis sera was also positive for HG factor activity. Our studies suggest that HG factor is an IgG antibody that may not be demonstrable by conventional IF methods, but which activates the classical complement pathway.

Erythema multiforme: direct immunofluorescence studies and detection of circulating immune complexes.

The immunologic parameters of 23 patients with erythema multiforme who were seen by us (17 patients) or who had biopsies sent for immunofluorescence testing (6 cases) are reviewed. Biopsy specimens were sectioned and tested with labeled antisera to human IgG, IgA, IgM, C3 and fibrin. Fourteen biopsies showed IgM deposits in the superficial blood vessels, 13 demonstrated C3, 15 showed fibrin deposition, and 1 biopsy showed IgA deposition. All biopsies were negative for IgG. Eight serum samples tested by indirect IF were negative for skin-reactive antibodies. In addition to IF testing, serum samples from 20 patients were tested for circulating immune complexes with a Clq binding radioassay and a monoclonal rheumatoid factor (mRF) inhibition assay. Immune complexes were not detected by the Clq binding assay, but 6 of 20 serum samples demonstrated low to moderate levels of immune complexes by the mRF inhibition assay. By sucrose density gradient ultracentrifugation in the mRF-reactive material in one serum sample sedimented in high molecular weight fractions and also demonstrated anticomplementary activity. These findings suggest that immune complex formation and subsequent deposition in the cutaneous microvasculature may play a role in the pathogenesis of erythema multiforme.

Leukonychia totalis, multiple sebaceous cysts, and renal calculi. A syndrome.

A 27-year-old man had leukonychia totals, multiple sebaceous cysts, and renal calculi. Pedigree analysis showed a total of four generations involved, with koilonychia additionally present in three of the affected individuals. Autosomal dominant inheritance is a postulation.

Bullous pemphigoid: a cause of peripheral blood eosinophilia.

A retrospective study demonstrated that fourteen of twenty-eight patients (50%) with clinical, histologic, and immunofluorescent findings of bullous pemphigoid had peripheral blood eosinophilia. Blood eosinophilia ranged from 5% to 43% when first tested, with increase in one patient to 56% during treatment. The pathophysiologic cause of blood eosinophilia in bullous pemphigoid is discussed with its relationship to previously demonstrated elevations of IgE and eosinophilic chemotactic factor of anaphylaxis (ECF-A) in serum and blister fluid. Peripheral blood eosinophilia was a common finding in our group of patients, and bullous pemphigoid should be included in the differential diagnosis of bullous skin conditions with eosinophilia.

An appraisal of routine direct immunofluorescence in vulvar disorders.

Sixty-four biopsies were obtained from patients with a variety of vulvar disorders for direct immunofluorescence study. Twelve of 24 vulvar biopsies from patients with lichen sclerosus demonstrated deposition of fibrin in the upper dermis, while 7 vulvar biopsies showed fibrin deposition at the dermal-epidermal junction. Blood vessel immunofluorescence was observed in several patients but was not a disease-specific finding. Patients with pemphigus and pemphigoid yielded characteristic reactions and served as positive controls. Direct immunofluorescence may be of value in assessing patients with vulvar disorders, and in particular lichen sclerosus.

Serum and blister fluid immune complexes in bullous pemphigoid: detection with C1q and monoclonal rheumatoid factor.

Eighty serum samples and 24 blister fluids from 51 patients with active bullous pemphigoid were tested for the presence of immune complexes by both a monoclonal rheumatoid factor (mRF) inhibition radioassay and a C1q-binding radioassay. Forty-two of the 80 serum samples were positive by the mRF assay, while 27 were positive by the C1q-binding assay. Antibody titres to the basement membrane zone did not correlate with levels of circulating immune complexes. Thirteen of 24 blister fluids had detectable immune complexes by the C1q assay, while only seven of 24 blister fluids were positive by the mRF assay. Sucrose density-gradient ultracentrifugation studies suggest that the mRF- and C1q-reactive substances in both bullous pemphigoid sera and blister fluids are of a size compatible with immune complexes. Although immune complexes are detectable in a high percentage of bullous pemphigoid patients, their role in this disease may be epiphenomenal rather than pathogenetic, merely reflecting the presence of autoantibody and soluble antigen.

Leukonychia totalis, multiple sebaceous cysts and renal calculi: a syndrome.

We have presented a family of 4 generations demonstrating total leukonychia. Multiple sebaceous cysts and renal calculi are associated features of the syndrome. Inheritance is autosomal dominant. We cannot determine whether renal glycosuria is a component of this syndrome.

Chromosomal breaks in T and B lymphocytes in Fanconi's anemia.

Three patients with Fanconi's anemia were analyzed for chromosome breaks. T and B cells were separated and grown in tissue culture with PHA and pokeweed antigen to ascertain the rates of breakage in these lymphocytic subpopulations. It has been found that there is no statistically significant difference in breakage rates in T and B lymphocytes. It is postulated that both T and B cells could be involved in the development of leukemia in Fanconi's anemia patients, assuming that chromosome breaks constitute a factor predisposing to the development of malignancy.