Eric R. Hurd

Immunoglobulin in Clinically Uninvolved Skin in Systemic Lupus Erythematosus ASSOCIATION WITH RENAL DISEASE

23 of 42, or 55%, of patients with systemic lupus erythematous had immunoglobulin deposits along the epidermal basement membrane of uninvolved skin (positive lupus band test [LBT]). In patients with low serum complement levels, 91% had a positive LBT), as compared with 15% in those with normal complement levels. The LBT was positive in 70% of patients with clinical and laboratory evidence of renal disease, but in only 31% of patients without renal disease. 81% of patients with the more severe histologic forms of lupus nephritis, i.e., proliferative glomerulonephritis and membranous glomerulonephritis, and positive tests, whereas only 23% with mesangial glomerulitis or normal histologic findings were positive. Immunoglobulins of the same class found in the skin were detected in the glomeruli of patients examined by renal biopsy. These results suggest that there is a relationship between the occurrence of immunoglobulin in the epidermal basement membrane and the presence of the more severe forms of lupus nephritis.

Virus antibody levels in systemic lupus erythematosus

Abstract Antibody titers to a group of viral antigens have been determined in sera from patients with systemic lupus erythematosus (SLE), control groups with inflammatory diseases and normals. Mean titers in SLE sera for all viruses tested were significantly greater than in four control groups, but not greater than in active tuberculosis, both by the complement‐fixation (CF) and hemagglutination‐inhibition (HI) methods. By the CF method, only measles virus showed significantly higher titers in SLE than in all control groups; by the HI method, measles antibody titers were higher in SLE than in all groups but tuberculosis. There was no correlation between antibody titers and gammaglobulin levels. The results indicated a moderate though variable overall hypereactivity in SLE to the viral antigens tested.

Localization of antigen-antibody complexes in intraarticular collagenous tissues.

The identification of immunoglobulins (IgG, JgA, IgM) and complement components (PI,,) in the surface layers of articular collagenous tissue biopsies (hyaline articular cartilage and menisci) of a high percentage of patients with rheumatoid arthritis (RA) is a novel finding. Their presence and biologic activity are as yet unexplained. The positive and specific immunofluorescent staining reactions for at least two immunoglobulins (Igs) and /I,,. found in sequential sections of the tissues of patients with classic RA suggest that these elements are in the form of immune complexes. Evidence has accumulated, in the antigen-induced arthritis of rabbits, used as a model for RA, that suggests that immune complexes in articular collagenous tissues might play a role in the pathogenesis of chronic inflammation.2, :i In the rabbit model, the injection of a soluble protein antigen into the knees of animals preimmunized with the antigen in complete Freunds adjuvant induces a chronic synovitis of long duration with histologic features that resemble those evident in the rheumatoid joint., In previous experiments, it was found that significant retention of radiolabeled inducing antigen only occurred in joints of specifically immunized animals. This antigen was identified in the surface layers of articular collagenous tissues (hyaline articular cartilage, menisci, and intraarticular ligaments) by autoradiographic and immunofluorescence techniques. The release of antigen from these tissues was protracted, with more than 70% of the total retained radioactivity found in articular collagenous tissues up to 6 weeks after induction.: In contrast, initially high levels of radioactivity in synovium were reduced 100-fold 1 week after injection and accounted for less than 0 .5% of persistent radioactivity in the joint at 6 weeks3, Rabbit Ig and the p,<. component of rabbit complement were identified by the immunofluorescence technique in exactly the same location as was antigen in these tissues.3 Further studies of Ig synthesis by arthritic synovium in short-term tissue cultures of membranes obtained at intervals u p to 6 weeks after induction indicated that between 30 and 40% of the newly manufactured Ig was specifically directed toward the inducing antigen.2 These data suggested that immune complexes of antigen, specific antibody, and complement persisted in articular collagenous tissues and were responsible for

Comparison of circulating T and B lymphocytes in discoid versus systemic lupus erythematosus

Absolute numbers of T and B lymphocytes were determined in groups of patients with discoid and systemic lupus erythematosus (LE) and in normal subjects. Patients with discoid LE had normal numbers of T cells but significantly increased numbers of B cells when compared with both the normals (P<0.05) and the systemic LE patients (P<0.001). The systemic LE patients had significantly decreased numbers of T cells when compared with the discoid LE patients (P<0.05) and with normals (P<0.005). From these studies it is concluded that discoid LE patients differ from systemic LE patients by having (1) normal numbers of T lymphocytes and (2) increased numbers of B lymphocytes. The role of T-B-cell imbalance in determining the expression of this disease is discussed.

The differential effects of cyclophosphamide and 6-mercaptopurine on the renal disease and skin immunoglobulin deposits of the NZB-NZW F1 hybrid mice

The following differential effects of immunosuppressive therapy with Cyclophosphamide (CYCLOPH) and 6-mercaptopurine (6-MP) in the female NZB-NZW F1 hybrid strain have been observed: (1) CYCLOPH but not 6-MP significantly decreased antinuclear antibody level. (2) Both CYCLOPH and 6-MP significantly decreased glomerular cell proliferation. (3) Both CYCLOPH and 6-MP significantly arrested progression of glomerulosclerosis. (4) While CYCLOPH significantly diminished Ig deposition in the glomeruli, 6-MP had no effect on this phenomenon. (5) While CYCLOPH decreased subepidermal globulin deposition in the skin, 6-MP appeared actually to enhance subepidermal staining. Thus, the present studies demonstrated that CYCLOPH was superior to 6-MP in four of the five parameters studied. In the case of one parameter, Ig staining of the skin, 6-MP actually produced enhancement of the staining. Both CYCLOPH and azathioprine which is a derivative of 6-MP, are currently being used for the treatment of human SLE. The present findings suggest that of the two, CYCLOPH may be the drug of choice.

Effect of 6-Mercaptopurine on Enzymes of the Polymorphonuclear Leuocyte∗

Summary Mononuclear cell infiltration of an egg albumin-induced skin lesion is preceded by infiltration with polymorphonuclear cells. In rabbits in which mononuclear cell infiltration of this lesion was suppressed by 6-MP, the possible effects of immunosuppression on the lysosomal enzyme content of the polymorphonuclear cells was investigated. The acid phosphatase, beta glucuronidase, and ribonuclease content of extracts of the polymorphonuclear cells of these animals were determined. In spite of adequate suppression of mononuclear infiltration of the induced skin lesion, no difference in the concentration of the three enzymes in the polymorphonuclear cells was noted. The results indicate that the failure of mononuclear cell infiltration in 6-MP-treated animals is not due to an effect on lysosomal enzyme synthesis in cells of the neutrophil series.