"Vasculitis look-alike" clinical syndromes.

Rheumatologists are sometimes asked to see patients with severe manifestations of vascular syndromes termed "pseudovasculitis," which often closely mimic autoimmune vasculitis. These syndromes include cholesterol embolism, fibromuscular dysplasia, antiphospholipid syndrome, ergotism, neurofibromatosis, and primary amyloidosis. In patients with suspected vasculitis, sometimes dramatic clinical findings may require urgent decision-making before all testing has been concluded. These circumstances make it particularly important for the clinician to consider pseudovasculitis in the differential diagnosis. Our review describes the common presentations of pseudovasculitis-which may include fever, weight loss, weakness, hypertension, and vascular occlusions-and emphasizes on their diagnostic features. A careful history and physical examination, laboratory and radiographic studies, as well as a high level of suspicion will help the clinician to consider pseudovasculitis in which treatment with immunosuppressive agents such as high dose corticosteroids or cytotoxic agents would be contraindicated and possibly disastrous.

Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules bearing lambda light chains.

In order to evaluate binding specificities of anti-F(ab')2 antibodies from patients with systemic lupus erythematosus (SLE) and from normal healthy controls, F(ab')2 fragments were prepared from 24 IgG myelomas with defined isoelectric points, DNA-associated idiotypes, and kappa/lambda light chain types. Using ELISA and hemagglutination assays, anti-F(ab')2 antibodies from 12 healthy controls and 29 SLE patients were observed to exhibit preferential binding (lambda > kappa) to myeloma F(ab')2 fragments composed of lambda light chains (P < 0.0001). No correlation of anti-F(ab')2 binding and presence of cationic, neutral, or anionic isoelectric points or for DNA-associated idiotypes on monoclonal F(ab')2 was detected. Anti-F(ab')2 antibodies, often elevated in SLE during remission, show preferential specificity for F(ab')2 fragments bearing lambda light chains.

Parallelism of serum anti-F(ab')2 and anti-cationic IgG reactivities in patients with systemic lupus erythematosus.

Cationic anti-DNA antibodies may be related to glomerular injury in murine lupus nephritis or in patients with systemic lupus erythematosus (SLE). Therefore, anti-cationic antibodies in SLE could include antibodies with regulatory function on such pathogenic cationic molecules. Since anti-F(ab')2 antibodies may be involved in the idiotype control of anti-DNA antibodies in some patients with inactive SLE, the present study was aimed to determine if SLE patients with significant serum levels of anti-F(ab')2 produce antibodies reacting with cationic IgG molecules. Three SLE sera with high titers of anti-F(ab')2 antibodies were individually adsorbed by sequential affinity chromatography on three Sepharose columns coupling normal IgG from Cohn Fraction II, pooled cationic IgG myeloma paraproteins displaying idiotypic anti-DNA markers (F4 and 8.12), and F(ab')2 fragment from allogeneic IgG, respectively. Eluates obtained from cationic IgG adsorption showed predominant anti-F(ab')2 reactivity. A similar profile was also detected in a serum from a normal control donor with high levels of anti-F(ab')2. Biotinylation of anti-cationic eluates showed that such antibodies were significantly more reactive with cationic than anionic or neutral IgG, confirming their apparent affinity for positively charged antigens on IgG molecules. Since anti-cationic absorptions were able to remove the anti-F(ab')2 activities in the SLE sera studied, it is possible that anti-cationic antibodies could function as immunoregulatory antibodies in the idiotypic control of some SLE autoreactive phenomena, including glomerular anti-DNA deposition.

Monoclonal antibodies against human anti-F(ab')2 antibodies react with light chain epitopes.

Anti-F(ab')2 antibodies affinity isolated from sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or normal SLE relatives were used to produce monoclonal antibodies (mAbs) in Balb/c and NZB mice. Four of five mAbs showed only primary light chain specificity. Only one mAb produced in an NZB mouse against anti-F(ab')2 from a single SLE patient showed anti-mu-chain specificity. Parallel identical control immunizations with IgG or a single human IgG kappa myeloma produced mAbs with a predominant gamma-chain/Fc fragment specificity. Anti-light chain specificity of mAbs was demonstrated to involve epitopes requiring tertiary structure of the entire light chain instead of antigens confined to Ckappa/lambda or Vkappa/lambda fragments. Anti-kappa specificity of three mAbs was extremely similar but not identical to that defined by anti-Km1 allotyping systems. No evidence was obtained with any of the mAbs produced for antigens unique to SLE or RA anti-F(ab')2 antibodies. The light chain antigenic prominence of many anti-F(ab')2 antibodies may reflect structural features shared by this group of immunoglobulins somehow important for their biologic function.

Laboratory tests for rheumatic diseases.

A carefully taken history and thorough physical examination remain the most crucial aspects of diagnosing rheumatic disorders. Non-rheumatologic conditions also need to be kept in mind. Laboratory tests should be looked on as mostly supportive or confirmatory, because many of the tests are relatively nonspecific and may lack sensitivity. If their limitations are recognized, however, the tests can be invaluable tools when the clinician confronts the task of differentiating an array of rheumatologic disorders.