Serum secretory immunoglobulins in ankylosing spondylitis

Summary Humoral mucosal immunity may be implicated in pathophysiology of ankylosing spondylitis (AS). The aim of the study was to evaluate serum levels of IgA, IgM and secretory IgA (sIgA), secretory IgM (sIgM) as well as free secretory component (FSC) in patients with AS compared to controls and rheumatoid arthritis (RA) patients.Levels of sIgA, sIgM and FSC were measured with a specific ELISA in 37 AS patients, 45 controls and 27 RA. The results were as follows: Serum levels of IgA were higher in AS vs controls and in RA vs controls (p=0.01). Levels of sIgA were higher in AS vs controls (p=0.01), but higher in RA vs AS (p=10^–4). There was no difference of sIgM in AS vs controls, FSC levels were higher in AS vs controls, and higher in AS patients with elevated CRP.In view of elevated FSC, this increase of sIgA in AS may have been due to excessive production of mucosal IgA after bacterial stimulation according to the current hypothesis of the disease.     

Immunological reactivity in ankylosing spondylitis. Circulating immunoblasts, autoantibodies, and immunoglobulins.

Circulating immunoblasts were studied in 39 cases of ankylosing spondylitis. The results were compared with 20 normal subjects and a group of 39 patients with rheumatoid arthritis, Immunoblasts were found to be increased in 11 patients with ankylosing spondylitis and in 22 patients with rheumatoid arthritis in contrast to the controls who were found to have a normal lymphoid cell population in the peripheral blood. Fifteen patients showed raised levels of one or more class of immunoglobulin. Autoantibodies, including antinuclear factors, were negative in all cases. There was a correlation between raised immunoblasts and plasma viscosity but not with clinical assessment of activity. The increase of immunoblasts in the peripheral blood, together with the raised immunoglobulins supports the suggestion of an immunological basis for ankylosing spondylitis.     

Raised serum creatine phosphokinase activity in ankylosing spondylitis.

Serum enzyme studies were made on 43 (37 male, 6 female) consecutive patients with ankylosing spondylitis. Serum creatine phosphokinase (CPK) activity was raised above 55 IU/l in 24 (65%) of 37 male patients (range 29-165 IU/l, mean 68) as compared with 2 (4%) out of 47 male controls (range 14-85 IU/l, mean 33: P less than 0-001); levels were greater than 35 IU/l in six (100%) out of six female patients (range 39-100 IU/l, mean 56) as against one (3%) of 35 female controls (range 3-106 IU/l, mean 16; P less than 0-001). The recognized pitfalls in interpreting CPK activity were avoided. In all of sixteen randomly selected patients isoenzyme studies confirmed that muscle is the source of the enzyme. There was a significant correlation between CPK activity and both spinal flexion and the reciprocal of finger-to-floor distance (P less than 0-5 in each case).     

Increased serum alkaline phosphatase activity in ankylosing spondylitis.

Raised serum alkaline phosphatase (AP) levels were found in 13 of 76 patients (17%) with ankylosing spondylitis (AS), and 11 of these 13 underwent further investigation to determine the origin of the increased enzyme activity. Three had levels within the normal reference range on re-estimation, and, of the remaining 8, AP isoenzyme studies indicated an increased liver fraction in 6. Serum gamma-glutamyl transpeptidase (GGT) was raised in only 3 patients. Increased AP activity did not appear to be directly related to disease activity or to drug therapy. These findings confirm the occurrence of increased serum AP activity in AS but challenge a previously reported suggestion that bone is the source of the increased enzyme.     

Sulphasalazine in ankylosing spondylitis.

In recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis. Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking. In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis. Evaluation after three months' treatment showed reduction of inflammatory activity and improvement of clinical variables. The side effects were mild. The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis.     

Association of inflammation with raised serum IgA in ankylosing spondylitis.

Serum immunoglobulins were measured in 122 patients with ankylosing spondylitis (AS) during various phases of disease activity and compared to those in 58 healthy subjects. The mean serum IgA was 38% higher in patients (306.9 mg/dl) than in controls (222.7 mg/dl) (P < 0.005), but there was no significant difference in IgG and IgM levels. Increased IgA was associated with laboratory parameters of active inflammatory disease. The mean IgA in patients having an erythrocyte sedimentation rate (ESR) equal to or greater than 15 mm/h was 369 mg/dl, 65% higher than in controls (P < 0.001), whereas there was no significant difference between controls and patients with an ESR of less than 15 mm/h. The mean IgA in patients having a C-reactive protein (CRP) level equal to greater than 15 micrograms/ml (15 mg/l) was 387.8 mg/dl, 74% higher than in controls (P < 0.001), and again there was no significant difference between controls and patients with CRP levels less than 15 micrograms/ml. (SI conversion: g/l = mg/dl x 0.01). It is suggested that selective increase of serum IgA occurs predominantly during phases of active inflammatory disease in AS, and this finding is compatible with the concept of a microbial triggering agent acting across an IgA secreting organ such as the gut.     

Employment in ankylosing spondylitis.

All patients with ankylosing spondylitis attending our rheumatology clinics were reviewed to assess the effect of their disease on employment. Back movement was measured in three planes, chest expansion determined, and peripheral joint involvement was noted to see whether these correlated with work capability. Sixty patients were reviewed (47 men, 13 women; mean disease duration 24.3 years). Nine were unemployed, but only four of these attributed this condition to ankylosing spondylitis. Although all four had severe neck, back, and hip involvement, this did not differentiate them from other patients who were fully employed. There was no relationship between disease duration and employment. The prospect for continued employment in ankylosing spondylitis is good even when the disease is long standing and severe.     

Antiglobulins in ankylosing spondylitis.

An immunoadsorption technique was used to investigate the presence of antiglobulin factors in 28 patients with ankylosing spondylitis and 30 healthy individuals. Both groups were "sero-negative" by standard agglutination techniques. Whereas the controls were consistently negative, 18 of the 28 patients with ankylosing spondylitis had antiglobulins of the IgG class.     

Juvenile ankylosing spondylitis.

We are beginning to understand the clinical nature of JAS, its relationship with other SSA, and factors involved in its pathogenesis. Clinical data may now allow early recognition of JAS through the identification of children with the SEA syndrome or chronic arthritis associated with the HLA-B27. Comparative clinical studies of the prevalence of the disease and the role of immunogenetic, racial and environmental factors are needed. It may be necessary to review current criteria for the diagnosis of JRA and to develop similar criteria for the diagnosis of AS in childhood and adolescence.     

Decrease in serum nucleotide pyrophosphatase activity in ankylosing spondylitis

OBJECTIVE: Ankylosing spondylitis (AS) is a prototype of a group of rheumatic diseases referred to as spondyloarthropathy. AS patients show marked ectopic ossification in the spine, occasionally resulting in so-called bamboo spine. Although a strong association with HLA-B27 has been reported, its aetiology remains undetermined. Another rheumatic disease, ossification of the posterior longitudinal ligament of the spine (OPLL), demonstrates ectopic ossification of the spinal ligaments very similar to that of AS. Recently, nucleotide pyrophosphatase (NPPS) was implicated in the aetiology of OPLL: an Npps mutation was found to cause OPLL in mice, and an association between a polymorphism of the human NPPS gene and OPLL was identified. The clinical similarities between AS and OPLL led us to hypothesize that NPPS may also be implicated in the aetiology of AS. To elucidate the role of NPPS in the pathogenesis of AS, we examined serum NPPS activity and the possible association of the NPPS gene with AS. METHODS: Forty-four Japanese patients with AS, 43 patients with OPLL, and age- and sex-matched normal volunteers took part in this study. We determined serum NPPS activity using high-performance liquid chromatography and examined the association between AS and NPPS using single nucleotide polymorphisms (SNPs) of the NPPS gene. RESULTS: Serum NPPS activity in AS patients was significantly decreased compared with the controls (P < 0.0001). However, there was no association between AS and NPPS gene SNPs. CONCLUSION: NPPS is implicated in the pathogenesis of AS.     

Detection of immune complexes in serum of patients with ankylosing spondylitis.

Immune complexes were measured in the sera of 18 patients iwth ankylosing spondylitis and 5 normal control subjects by their ability to inhibit antibody-mediated lymphocyte-induced cytotoxicity. 11 of the spondylitis and none of the control sera contained circulating complexes. Fractionation of sera on Sephadex G-200 showed that complexes were of two molecular sizes, one of intermediate and the other of large molecular weight. The presence of immune complexes did not correlate with activity of disease or the presence of peripheral arthritis although the one patient with polyarthritis had the highest level of complexes detected in this study. The nature of the antigen in these antigen-antibody complexes is of great interest since it may provide evidence of the aetiological agent in the disease.     

Myocardial dysfunction in ankylosing spondylitis.

Echocardiographic evidence has suggested abnormalities of the myocardial function in patients with ankylosing spondylitis. In this work the cardiac function in patients with ankylosing spondylitis and in normal volunteers was evaluated. Twenty four normal volunteers and 21 patients with ankylosing spondylitis aged 18-45 were studied. None had overt cardiac disease. Cardiac function was assessed at rest with echocardiography, at rest and during supine bicycle exercise using radionuclide angiography in the left anterior oblique position following equilibration with 740 MBq of technetium-99. The subjects undertook supine bicycle exercise with 30 W increments every three minutes to the point of fatigue. Comparison of data from normal volunteers and patients with ankylosing spondylitis were made using Student's t test for independent samples or the Mann-Whitney non-parametric technique, as appropriate. Subjects were matched for age, sex, height, and weight. There were no echocardiographic differences; however, global nuclide left ventricular function showed several differences between normal volunteers and patients with ankylosing spondylitis. The peak filling rate during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 6.5 (SD 1.2); patients with ankylosing spondylitis 5.7 (1.2). The time to reach peak filling during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 102 (22); patients with ankylosing spondylitis 120 (23). Regional analysis also showed differences between patients with ankylosing spondylitis and normal volunteers both at rest and during exercise. In the anteroseptal region the filling fraction and peak filling rate were significantly lower in patients with ankylosing spondylitis. Most of the differences (although not all) were in the variables of diastolic function. This study shows that there are subtle abnormalities in cardiac function in patients with ankylosing spondylitis. The major abnormalities are in the diastolic function, suggesting a decrease in left ventricular compliance.     

Bronchoalveolar lavage in ankylosing spondylitis.

Bronchoalveolar lavage and bronchial biopsies were performed in 15 patients with ankylosing spondylitis (AS) and 17 control subjects. There was no difference in total cell count, number of lymphocytes, CD4+/CD8+ ratio, or beta 2 microglobulin concentrations in bronchoalveolar lavage fluid between these two groups. Bronchoalveolar lavage IgA concentrations were not increased, but bronchial IgA deposits were more common in AS. This study failed to show any subclinical alveolitis in AS.     

Echocardiographic abnormalities in ankylosing spondylitis.

Twenty four patients with ankylosing spondylitis of 10 or more years' duration were assessed for evidence of cardiac disease. Seven patients (29%) had evidence of cardiac disease, including one patient with a pericardial effusion, three with conduction abnormalities, and two with aortic incompetence. Aortic incompetence in one patient was clinically silent and was detected only with Doppler echocardiography. This patient had, in addition, thickening of the posterior aortic wall, an echocardiographic feature not previously described in ankylosing spondylitis. There was no evidence of aortic valve disease in a control group matched for age and sex. Patients with ankylosing spondylitis and cardiac abnormalities were older, had a longer disease duration, and more peripheral joint disease than those without cardiac abnormalities. Doppler echocardiography is a useful technique in the assessment of cardiac disease in ankylosing spondylitis and may detect aortic valve disease at an early preclinical stage.