C. Kirk Osterland

Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus.

Abstract Immune responses to hydralazine were detected in patients with hydralazine-induced lupus but not in patients taking hydralazine without developing toxicity, patients with systemic lupus er...

Abnormalities of Delayed Hypersensitivity in Systemic Lupus Erythematosus

Abstract Abnormalities of delayed hypersensitivity were found in patients with active systemic lupus erythematosus (SLE). The following immune responses were noted in 39 patients with SLE compared to 30 normal controls: (1) delayed hypersensitivity skin test responses to purified protein derivative (PPD) and trichophyton were significantly reduced in the patients with SLE, (2) in vitro lymphocyte transformation to PPD was normal, (3) the majority of patients with SLE had circulating antibodies to native deoxyribonucleic acid (nDNA), (4) these patients did not exhibit increased skin test responses or lymphocyte transformation to nDNA. The impairment in delayed hypersensitivity to PPD and trichophyton suggests that skin testing with PPD is inadequate to screen patients with SLE for tuberculosis. Furthermore, frequent infections which occur in some patients with SLE may result in part from their impaired cellular immune responses. The dissociation between skin response and lymphocyte transformation to PPD suggests that defects in cellular immunity may be selective. The dissociation between humoral and cellular immunity to nDNA suggests that control mechanisms exerted on one or both of these responses may be defective in SLE.

Autoantibodies in chronic pulmonary tuberculosis

Abstract Sera from patients with chronic pulmonary tuberculosis have been examined for abnormal antibody activity. A very high frequency of several autoantibodies was discovered. The incidence of 46.6 per cent for antinuclear factor did not seem to bear an absolute relationship to drug therapy or disease duration. Rheumatoid factor activity, and a factor responsible for a peritubular staining pattern in the immunofluorescent test with mouse kidney were also present. It is suggested that factors besides drugs, such as tissue breakdown, chronicity, and adjuvant effect of mycobacteria may play a role in this anti-tissue antibody production in tuberculosis.

Transient monoclonal proteins in drug hypersensitivity reactions

Two patients were studied in whom monoclonal (M) immunoglobulin G (IgG) proteins developed during the course of a serum sickness-like drug hypersensitivity reaction to cloxacillin (Orbenin) and sodium cephalothin (Keflin), respectively. The clinical evidence and time sequence of events support this association. In both patients there was evidence of an active antibody response to the given antibiotic and to the benzylpenicilloyl group as well. However, protein fractions obtained by agar gel preparative electrophoresis failed to show a higher antibody concentration where the M peak was located, and absorption experiments performed with penicillin G-, cloxacillin- and cephalothin-coated red cells failed to absorb these M proteins. These transient paraproteins can be seen in association with antibiotic(s) administration in the context of a hypersensitivity reaction and do not apparently represent a specific immune response.

Studies on carbohydrate localization in human γM-globulin

Abstract Human γM globulin contains at least three chemically distinct carbohydrate groups. Two are on the heavy chain and one is on the light chain. To further localize the heavy chain carbohydrate groups, the heavy chain was fractionated by CNBr. The two carbohydrate moeties were found on separate CNBr fragments. One fragment, which contained the largest carbohydrate subunit, contained 84 residuesincluding the H-L disulfide bond. This was determined by selectively labeling this bond with 14C-iodoacetamide. This carbohydrate also was probably located in the Fc portion, which makes the Fc of macroglobulin approximately 25 per cent carbohydrate. The other carbohydrate group was found on a large CNB fragment which contained 148 residues. This fragment is probably in the Fd portion of the heavy chain.

A Unique lymphoproliferative disorder associated with an IgM platelet agglutinin, diffuse hypergammaglobulinemia, amyloid deposition and excessive urinary excretion of IgG fragments

Abstract A case is reported of a lymphoproliferative disorder with autoimmune hemolytic anemia and thrombocytopenia. Platelet agglutinins were demonstrated to be 19S gamma macroglobulins, a unique observation. The disease was initially manifested by lymphocyte and reticulum cell proliferation, and eventually by plasma cell proliferation with amyloid deposition. The patients serum exhibited extreme diffuse hypergammaglobulinemia with an increase in both IgG and IgM components. The urine was remarkable for its high content of kappa and lambda light chains, Fd-like fragments and Fc-like fragments. The interrelationships between the pathologic findings and protein abnormalities are briefly discussed and compared with the lymphoma associated dysproteinemias reported in the literature.

Release of a low molecular weight Fc-like fragment on reduction of water-insoluble IgG myeloma proteins.

Abstract. Serum from a patient with multiple myeloma exhibited an unusual concurrence of abnormalities: (1) bitypic gammopathy consisting of a whole Λ‐IgG 1 paraprotein plus a circulating Λ‐Bence Jones protein; (2) marked insolubility of the partially purified paraprotein under conditions of low ionic strength, but good solubility upon further purification; (3) release of an unusual low molecular weight fragment containing Fc antigenic determinants under standard conditions of mercaptoethanol reduction of the purified paraprotein. Evidence is presented supporting the origin of the Fc fragment from the paraprotein heavy chain and describing the requirement for 6 M urea for its dissociation from the reduced and alkylated heavy chain. The phenomenon is evidently not rare, since screening of 14 additional myeloma sera revealed one with similar euglobulin properties and an apparently similar Fc fragment abnormality. The nature and origin of the fragment in relation to previously described immunoglobulin fragments are discussed.