Systemic lupus erythematosus and common variable panhypogammaglobulinemia: a patient with absence of circulating B cells.
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Biomedical subjects
Publications and source records attributed to J Karsh.
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Fibronectin (Fn) was detected in 12/14 2.5% polyethylene glycol precipitates of rheumatoid serum positive for rheumatoid factor (RF). This association led to an investigation of the capacity of Fn to interact with IgM RF and heat aggregated human IgG. Our data suggest that Fn can interact directly with both of these substances at a site in the Fc fragment of the immunoglobulin molecule. The exact cite of the interaction is still to be defined but evidence indicates that it is probably distinct from sites binding staphylococcal protein A and complement.
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Immunogenicity of 14 valent pneumococcal vaccine was evaluated in a placebo controlled, double blind, randomized study involving 77 patients with systemic lupus erythematosus (SLE). Antibodies to 12 type specific capsular antigens were measured prior to and one and 6 months post injection. In 17 patients treated with prednisone plus cyclophosphamide and/or azathioprine, mean body concentrations (ng antibody nitrogen/ml serum) increased from 528 to 1328 and 852, respectively, in vaccinated patients compared to 307, 308 and 344 following placebo. In 60 patients not receiving immunosuppressives, mean antibody concentrations were 355, 1361 and 920 post vaccine and 401, 473 and 377 post placebo. Our study demonstrates that antibody responses to pneumococcal vaccine in SLE patients is unaffected by these immunosuppressive agents.
Joint mobility was assessed in 80 consecutive adult noninsulin-dependent diabetic (NIDD) patients and 47 nondiabetic controls matched for age and sex. Impairment of mobility was observed in 36 NIDD patients but only 7 controls (p less than 0.01). There was no significant differences between diabetic patients with and without impaired mobility with regards to age, duration of diabetes, mean daily insulin dose, or overall diabetic control as assessed by the measurement of glycosylated haemoglobin (HbA1C). However, NIDD patients with impaired joint mobility had a significantly increased frequency of microvascular disease, as shown by retinopathy and/or nephropathy (42% versus 22%, p less than 0.05), were more often on insulin treatment (86% versus 63%, p less than 0.05) and more frequently had additional rheumatic disorders such as Dupuytren's contracture and osteoarthritis (36% versus 18%, p less than 0.05). In addition tight waxy skin over the phalanges was commonly associated with impaired mobility (58% versus 22%, p less than 0.01). Limitation of joint mobility was most prominent in the hands but caused no functional impairment. This finding may be an additional marker of microvascular disease in the adult diabetic patient.
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Immune complexes were precipitated with polyethylene glycol (PEG) from sera of patients with rheumatoid arthritis (RA), psoriatic arthritis and systemic lupus erythematosus. Precipitates were tested for their capacity to consume complement and for the presence of fibronectin (Fn) and specific autoantibodies rheumatoid factor (RF, anti-DNA). The results showed enrichment of autoantibody activity in the precipitates. In RA, RF was especially enriched in 2.5% PEG precipitates, while IgM anti-DNA activity was more evident in 3.5% precipitates. IgG anti-DNA antibody was detected only in 3.5% precipitates from lupus sera. Complement consumption activity of precipitates was mainly related to IgM autoantibodies. There was a strong correlation between the presence of RF activity and Fn in the PEG precipitates. Nephelometric studies revealed direct interaction between the Fn and IgM RF or heat aggregated gammaglobulin. It may be possible to monitor the serum levels of immune complex material using PEG precipitation.
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Serum concentrations of anti-DNA and anti-deoxyribonucleoprotein (NP) antibodies were measured in parallel by standardized ELISA methods with a polyvalent anti-immunoglobulin conjugate in patients with systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and rheumatoid arthritis (RA). High levels of these antibodies predominated in systemic lupus erythematosus. While an appreciable incidence of antibodies also occurred in SS and RA, they were mostly at lower levels. By using heavy chain-specific anti-immunoglobulin conjugates, IgG antibodies to both DNA and NP were found in SLE more frequently and at higher levels than were IgM antibodies. In contrast, IgM antibodies to DNA and NP predominated in SS and RA. The immunoglobulin class of the anti-DNA and anti-NP responses in a given SLE patient were not infrequently different. For example, a patient might show a very high IgG but low IgM anti-DNA value, with the reverse being true for anti-NP. IgG anti-DNA antibodies were significantly associated with depressions of C3. During changes in SLE serology, normalization of DNA binding by Farr radioimmunoassay and/or complement was most frequently associated with normalization of the IgG anti-DNA antibody concentrations. In patients simultaneously possessing elevated levels of anti-DNA, anti-NP and rheumatoid factor (RF), absorption with aggregated human IgG usually decreased only the RF activity. In some, however, such absorption decreased all three antibody values simultaneously. The latter findings support observations that some RF possess antinuclear properties.
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From November 1977 through June 1979, 26 of 28 nonuremic patients had forearm arteriovenous fistulas successfully created for dialysis, lymphapheresis or vascular access. To improve patency, aspirin and heparin therapy was begun the night before operation and continued postoperatively in all except one patient. No major change in coagulation parameters resulted from this treatment. Twenty-five radial artery to cephalic vein fistulas were created in 23 patients, brachial artery to basilic vein fistulas in 3 patients, and 8 mm polytetrafluoroethylene brachial artery to basilic vein loop grafts in two patients. Early fistula failures (within 11 days) required thrombectomy once in four patients and twice in another patient. A sixth patient was not given heparin or aspirin and required multiple thrombectomies before the graft was removed because of infection. One other patient refused further surgery after two unsuccessful attempts to create an arteriovenous fistula. In the remaining 26 patients, the fistulas have been successfully maintained, and in 18 patients more than 214 dialysis or lymphapheresis treatments have been performed without problems. The successful establishment of arteriovenous fistulas in nonuremic patients has been achieved by giving aspirin and low dose heparin therapy, which appears to be an integral step in maintaining patency.
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The incidence of pulmonary emphysema in patients with alpha-1-antitrypsin (alpha-1-AT) deficiency associated with the protease inhibitor (Pi) phenotype ZZ is increased. To determine whether less severe deficiency states of alpha-1-AT (i.e. Pi phenotypes other than ZZ and MM) might predispose to the development of pulmonary disease, Pi phenotypes were determined in a group of patients in whom the incidence of chronic pulmonary disease is high. The proportion of 52 patients with Sjögren's syndrome who had Pi phenotypes other than ZZ and MM was not significantly greater than that for populations of normal subjects. Mean values for tests of pulmonary function, including estimates of both restrictive lung disease and airway obstruction in patients with the MM phenotype were not significantly different from corresponding means for patients with non-MM phenotypes. These findings suggest that the increased susceptibility of patients with Sjögren's syndrome to develop chronic obstructive pulmonary disease is not attributable to an abnormally high frequency of non-MM phenotypes and associated moderately reduced serum levels of alpha-1-AT.
Simple, rapid, quantitative, and reproducible ELISA procedures were developed for the determination of antibodies to DNA and NP in human sera. The results are reported in International Units per milliliter, based on the WHO reference preparation of anti-nuclear factor serum. The results of both tests are significantly correlated with anti-dsDNA values obtained by an RIA (Farr technic) and by the Crithidia luciliae IF assay. The anti-DNA and anti-NP ELISA test results were more frequently positive in SLE sera than were screening tests for anti-dsDNA by the Crithidia procedure or anti-NP detection by a latex agglutination test. Parallel tests in 284 sera from patients for anti-DNA and anti-NP by ELISA showed a significant correlation between the two antibody values. However, 17% of the specimens were positive for antibodies to one antigen but not the other, whereas other specimens showed a strong predominance of one antibody over the other. Absorption studies confirmed the differing antibody specificities measured by the two assays. The ELISA anti-DNA results were inhibited by native DNA, NP, and denatured DNA in increasing order of efficiency. In contrast, the antibodies against NP were strongly inhibited by NP but only very slightly by dsDNA or denatured DNA. Other antigens, including histones, ribonucleic acid, extractable nuclear antigens, and aggregated human IgG, inhibited only slightly or not at all in either assay.
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Thirty-two patients with Sjögren's syndrome were randomly selected to receive either multivalent pneumococcal polysaccharide vaccine or saline placebo in a double-blind study. Among placebo treated patients, levels of antipneumococcal antibodies remained constant. Immunized patients developed significant elevations of antibody concentrations against all 12 capsular serotypes measured. Levels fell, but persisted above baseline, for 8 of the serotypes 6 months after immunization. During the 6-month study no clinical or serologic evidence of disease exacerbation occurred in either group. We conclude that pneumococcal vaccine can be safely and successfully administered to patients with Sjögren's syndrome.
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