Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here...
Cellular and humoral immune responses have been measured in patients with Sjøgren's syndrome with, and without, rheumatoid arthritis, patients with sero-positive and sero-negative rheumatoid arthritis, and a control group of patients. Several patients with sero-positive rheumatoid arthritis and patients with Sjøgren's syndrome complicated by rheumatoid arthritis failed to respond to 2–4 Dinitrochlorobenzene, and exhibited poor secondary responses to tetanus toxoid. Mantoux responses, however, were diminished only in patients with the sicca syndrome. Estimation of RNA/DNA ratios of peripheral blood lymphocytes showed increased ratios in those groups of patients responding poorly to DNCB and tetanus toxoid. As the lymphocyte RNA/DNA ratio is correlated to mean lymphocyte diameter, this means that patients with elevated ratios have an absolute, or relative, increase in the number of large lymphocytes circulating in the peripheral blood. It is suggested that failure to respond to DNCB may be due to a deficiency of uncommitted small lymphocytes.
No correlation between the occurrence of the salivary duct antibody and focal lymphocytic sialadenitis in the labial mucosa was found in ten patients with the sicca syndrome, twenty-seven patients with Sjøgren's syndrome and rheumatoid arthritis, and forty-seven patients with rheumatoid arthritis alone. No correlation between the variables was found in any of the groups examined. Post-mortem studies on the labial mucosal biopsy show that the results of biopsy are reproducible, and so the lack of correlation is not due to sampling error when the biopsy is taken. It is suggested that the salivary duct antibody is an epiphenomenon of rheumatoid arthritis rather than a manifestation of Sjøgren's syndrome per se.
Inter-relationships of biochemical and immunological tests of liver function have been studied in a prospective study of 216 patients with rheumatoid arthritis (RA), 32 patients with Sjogren's syndrome, and 27 patients with the sicca syndrome, and these results have been compared with those obtained 289 patients with osteoarthrosis or with a form of seronegative polyarthropathy. In general the prevalence of abnormalities in serum alkaline phosphatase, bromsulphthalein excretion, smooth muscle antibody, and mitochondrial antibody in the former three groups was higher than in patients with osteoarthrosis. Patients with Sjogren's syndrome with RA had a higher prevalence of abnormalities of bromsulphthalein excretion, salivary duct antibody than patients with the sicca syndrome. Patients with RA had a higher pervalence of rheumatoid factor than those with the sicca syndrome. Patients with a positive smooth muscle or mitochondrial antibody were found to have a higher prevalence of hepatomegaly and splenomegaly, of abnormal liver function tests, of other autoantibodies, and of histological abnromalitis of liver than those in whom these tests were negative.
This study investigated the overall clinical impact of anti-α-actinin antibodies in patients with pre-selected autoimmune diseases and in a random group of anti-nuclear antibody (ANA)-positive individuals. The relation of anti-α-actinin antibodies with lupus nephritis and anti-double-stranded DNA (anti-dsDNA) antibodies represented a particular focus for the study. Using a cross-sectional design, the presence of antibodies to α-actinin was studied in selected groups, classified according to the relevant American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) (n = 99), rheumatoid arthritis (RA) (n = 68), Wegener's granulomatosis (WG) (n = 85), and fibromyalgia (FM) (n = 29), and in a random group of ANA-positive individuals (n = 142). Renal disease was defined as (increased) proteinuria with haematuria or presence of cellular casts. Sera from SLE, RA, and Sjøgren's syndrome (SS) patients had significantly higher levels of anti-α-actinin antibodies than the other patient groups. Using the geometric mean (± 2 standard deviations) in FM patients as the upper cutoff, 20% of SLE patients, 12% of RA patients, 4% of SS patients, and none of the WG patients were positive for anti-α-actinin antibodies. Within the SLE cohort...
Cryoproteins were isolated from the serum of 5 patients with essential cryoglobulinaemia 5 patients with rheumatoid arthritis, and 2 patients with Sjøgren's syndrome. These cryoprecipitates contained IgG, IgM, and IgA as well as complement proteins C1q, C4, C3, and factor B. The cryoprecipitates were analysed further for content of antibody and antigen, and were tested for their ability to activate complement. In the cryoprecipitates of 2 patients with Sjøgren's syndrome, nuclear antigen and antinuclear antibody characteristic of an immunological specificity found in Sjøgren's syndrome were shown. The cryoprecipitates of 6 other patients contained rheumatoid factor and antibody to a lymphocyte nuclear antigen. The solubilized cryoprecipitates were tested by in vitro assays for their ability to activate complement by the classical or alternative pathways. All 12 cryoprecipitates activated the classical pathway. 9 of the 12 cryoprecipitates also activated the alternative complement pathway under conditions which did not involve activation of C1 and C4. These studies show that a high percentage of cryoprecipitates consist at least in part of immune reactants. We discuss the relationship of these findings to pathogenetic mechanisms in disease.
The clinical significance of antinative DNA antibodies as measured by the Farr test was investigated in 10 patients with the articular features of rheumatoid arthritis. 5 of these patients also satisfied criteria for a diagnosis of systemic lupus erythematosus (SLE) and might be classified as rheumatoid/lupus overlap syndromes or as rheumatoids with systemic complications. None had evidence of renal disease and 3 of the 5 had Sjgøren's syndrome. The sixth patient had aggressive peripheral arthritis, alopecia, and Sjøgren's syndrome and developed anti-DNA antibodies after treatment with penicillamine. All of the 4 rheumatoid patients with no clinical features typical of SLE had some special disease feature. The first had subclinical liver disease and the other 3 had Sjøgren's syndrome in addition to localized vasculitic skin ulceration (2) and pulmonary fibrosis (1).
A patient with Sjøgren's syndrome developed renal tubular acidosis which led to systemic acidosis and potassium depletion. Treatment with Shohl's solution and potassium supplements was followed by subjective improvement in tear flow, salivary flow, and by disappearance of bronchitic symptoms. Detailed objective assessments were then made during the next year, twice on treatment and twice without. These confirmed the subjective impression of improvement.