Antibodies and vascular involvement in inflammatory joint disease: clinical relevance

The vascular endothelium is a common target of inflammatory joint disease. Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome can be responsible for a spectrum of vascular disorders that encompasses vasculitis, thrombosis and/or atheroma associated with the antiphospholipid syndrome, and vascular damage caused by cryoglobulin deposition. These mechanisms can coexist, particularly in lupus patients. Joint disease is sometimes the presenting manifestation in primary vasculitis. Autoantibodies are detectable in most patients with vascular involvement and inflammatory joint disease. They are not merely markers for vascular involvement: in vitro and in vivo data suggest that some autoantibodies may contribute to the genesis of endothelial lesions, together with other factors. For instance, evidence of pathogenic effects has been found for antineutrophil cytoplasmic antibody (ANCA), most notably with antimyeloperoxidase or antiproteinase-3 specificity, in small-vessel vasculitides (Wegener's granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis); for immune complexes, particularly those containing cryoglobulins, in vasculitides secondary to CTDs; and for circulating anticoagulant and anticardiolipin antibodies, above all anti-beta2-glycoprotein I, in antiphospholipid syndrome. Antibodies to annexin V, modified lipoproteins, and endothelial cells may be of interest; their clinical relevance is unclear, however, and no standardized assays are available, so thatthese antibodies are not looked for in everyday practice. When deciding which antibody tests should be performed in a given patient, the circumstances surrounding the onset of the vasculopathy should be borne in mind. In patients with previous CTD, the tests are selected based on the diagnosis. In contrast, in a patient with no previous diagnosis, a vasculopathy can be either primary or secondary to undiagnosed CTD or to antiphospholipid syndrome: consequently, a broader array of tests is needed in this situation.