Assessment of class-specific antibodies against denatured DNA in patients with systemic lupus erythematosus.

In this retrospective study 103 serum samples from 16 females with systemic lupus erythematosus (SLE), obtained during a mean follow-up time of 2 years, were investigated for the presence of anti-denatured [single-stranded (ss)] DNA antibodies of the IgG, IgM, and IgA classes. The anti-ssDNA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA), and the results were expressed in three ways: as units derived from a single serum dilution and as two parameters, E and A, calculated from the dose-response curve, E being an estimate of the effective amount of antibodies and A a function of the reaction constant between the antigen and the antibody. The simultaneous occurrence of anti-ssDNA antibodies of all three immunoglobulin classes was seen most often in the patients with the shortest duration of the disease. Clinically active disease was found to correlate with high reaction constants of the IgA anti-ssDNA antibodies. There was also an association between the IgA anti-ssDNA antibody levels and the presence of nephritis. Great fluctuations in the amounts of effective antibodies of the IgG class were seen in seven patients, in six of whom changes in the disease activity also were seen. Changes in the disease activity were unaccompanied by fluctuations in the IgG anti-ssDNA levels in four patients; two of these patients were positive for antibodies against extractable nuclear antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Triggering infections in reactive arthritis.

Certain microbes like yersinia, salmonella, shigella, campylobacter, chlamydia, and possibly gonococcus can trigger reactive arthritis especially in patients of the HLA-B27 type. In the present study we have used serological and culture methods to identify the probable triggering infection in 50 consecutive HLA-B27 positive patients diagnosed as having reactive arthritis. The two most common triggering agents thus identified were Yersinia enterocolitica (12 patients) and Chlamydia trachomatis (11 patients). In addition six patients had high antistreptolysin O titres and two high teichoic acid antibody titres suggesting group A streptococci and Staphylococcus aureus as triggering agents. In 13 patients no preceding infection could be identified. The identity of the infective agent seems to have very little effect on the clinical picture of the reactive arthritis - the only difference between the various aetiological groups in the present material was absence of fever in the patients with a preceding C. trachomatis infection, of whom only one out of 11 had a temperature greater than or equal to 38 degrees C, whereas 13 of 16 patients with a preceding enterobacterial, and five of the eight patients with a streptococcal or staphylococcal infection had raised temperatures.

Circulating immune complexes in Yersinia infection.

The occurrence of circulating immune complexes (CIC) was studied in 9 patients with Yersinia arthritis and 7 with Yersinia enteritis (YE) without extraintestinal symptoms by the platelet-iodinated protein A (PIPA) technique and by a solid phase Clq-binding enzyme-linked immunosorbent assay. CIC were detected by both techniques in all the patients with Yersinia arthritis during the acute disease and in 3 of them after recovery. CIC were also found in 5 of the 7 patients with uncomplicated YE, suggesting that CIC were associated with YE irrespective of the development of arthritis.

Enhanced neutrophil migration in vivo HLA B27 positive subjects.

Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell counts. The present results give credence to the view that the hyperreactive neutrophils and the vasodilatory prostaglandins produced by them can together trigger a vicious circle which results in increased inflammatory symptoms in patients with yersinia arthritis who have HLA B27 as compared with those who lack this antigen.

Bilateral renal artery dissections: unusual complication of polyarteritis nodosa.

A case of polyarteritis nodosa with the acute complications of multiple bilateral real artery dissection, perirenal haemorrhage and kidney infarction is described. The diagnosis of polyarteritis nodosa was established on the basis of angiographical and clinical findings. Follow-up arteriograms and CT-findings after prednisone therapy are discussed.

Neutrophil function and HLA-B27.

The pathogenesis of HLA-B27 linked diseases, including reactive enteroarthritides, is not known. Differences in immune response, cross-reaction between microbial antigens and host cell structures, attachment of microbial components on the host cell surfaces with subsequent autoimmune reaction, and inflammatory responsiveness of the host may be involved. In this contribution we present evidence to show that HLA-B27 positive subjects may be prone to an exaggerated inflammatory response, as compared with HLA-B27 negative subjects.

Occurrence of antibodies to teichoic acid in patients with diseases other than staphylococcal infection.

To determine the usefulness of the teichoic acid antibody (TAA) test in conditions where unspecific viral and bacterial antibodies are often encountered, we measured TAA by the gel-diffusion method in 475 patients without known staphylococcal disease; they included 213 patients with arthritis, 108 with liver diseases, 100 with gastro-intestinal disorders and 54 with acute pharyngitis. Positive controls were 104 patients with Staphylococcus aureus bacteraemia and 203 healthy adults were negative controls. Thirteen (6%) of the healthy adults had positive TAA titres (greater than or equal to 4), and the highest titre was 8 in two people (1%). Positive titres were found in 38% of patients with S. aureus bacteraemia and high titres (greater than or equal to 8) were seen in 24%. Among the patients with arthritis, positive TAA titres were found significantly more often than in healthy controls in patients with Yersinia arthritis (p less than 0.01) and systemic lupus erythematosus (SLE; p less than 0.02). In other patient groups, the percentage of positive TAA titres did not differ significantly from that in healthy adults. Eight (2%) of the 475 patients without known staphylococcal infection had TAA titres greater than or equal to 8 but these high titres were not associated with any particular disease group. Only two of these eight patients had slightly raised antibody to staphylococcal alpha-haemolysin. We conclude that the TAA test cannot be used as a reliable indicator of septic staphylococcal disease in patients with Yersinia arthritis or SLE, but that in general, TAA titres greater than or equal to 8 point strongly to S. aureus infection even in patients with autoimmune or liver diseases.

Effect of dichloromethylene diphosphonate (Cl2MDP) on immune function in breast cancer patients with bone metastases.

Immune function was studied in normocalcemic breast cancer patients with bone metastases treated with either dichloromethylene diphosphonate (Cl2MDP) or placebo. The results showed no significant difference between the two patient groups. This suggests that Cl2MDP does not markedly impair the host's defense mechanisms, and in this respect can be safely used in the treatment of patients with resorptive bone disease.

Chemotaxis in yersinia arthritis. In vitro stimulation of neutrophil migration by HLA--B27 positive and negative sera.

Chemotactic and chemokinetic migration of polymorphonuclear leukocytes in sera from patients with previous yersinia arthritis and from healthy subjects with or without HLA--B27 were studied by the leading front method. Irrespective of yersinia arthritis, zymosan-activated sera from subjects who were HLA--B27 positive were significantly more chemokinetic than were HLA--B27 negative zymosan-activated sera from healthy control subjects. The chemotactic activities of zymosan-activated sera that were HLA--B27 positive or negative, as determined by chemotactic increments, were much the same. The results suggest that zymosan-activated serum that is HLA--B27 positive stimulates random migration of polymorphonuclear leukocytes, but not their directional migration, more than does HLA--B27 negative serum that has been zymosan activated. This may contribute to accumulation of polymorphonuclear leukocytes at the site of inflammation in vivo and thereby to inflammatory symptoms in yersinia arthritis patients with HLA--B27.

Followup study on patients with Reiter's disease and reactive arthritis, with special reference to HLA-B27.

An analysis of 160 patients with Reiter's disease, 144 with yersinia arthritis, and 9 with salmonella arthritis was performed, Complete or incomplete Reiter's syndrome was observed in one-third of the patients with yersinia arthritis and in most of those with salmonella arthritis. During the followup period, chronic back pain and joint symptoms were frequent in all the patient groups. Patients who were HLA-B27 positive had a more severe acute disease (more frequent back pain, urologic symptoms, mucocutaneous manifestations, and a longer duration of the disease) and more frequent chronic back pain and sacroiliitis.

Neutrophil chemotaxis under agarose: a statistical analysis and comparison of the chemotactic response of cells from different donors.

Distance of migration and cumulative cell count were determined in parallel to quantitate migration of polymorphonuclear leukocytes (PMNs) of healthy volunteers in the chemotaxis-under-agarose assay. The cumulative percent distributions of the rates of spontaneous migration in the absence of an attractant, of chemokinetic migration in zymosan-activated human serum (ZAS) incorporated in agarose, and of chemotactic migration toward ZAS were approximately normal. Cord blood PMNs are known to respond poorly to ZAS in vitro; this was used to determine whether the chemotactic indices (CI: ratio of migration toward ZAS to spontaneous migration) and the chemotactic differentials (CD: difference between migration toward ZAS and spontaneous migration) correlated with impaired chemotaxis under agarose. Both CI and CD values of cord PMNs were significantly low, indicating a positive correlation. The CI values of healthy volunteers correlated negatively with spontaneous migration, whereas the correlation of the CD values was neither negative nor positive. Since spontaneous migration of PMNS varies, the results support the use of CD values when comparing chemotactic responses of PMNs from different donors; e.g., the CD values were determined to evaluate the responsiveness of HLA-B27-positive PMNs, which we recently found to migrate under agarose toward ZAS more than HLA-B27-negative PMNs. The CD values of HLA-B27-positive PMNs were significantly high, indicating that the cells were high responders.

Chemotaxis in yersinia arthritis. HLA-B27 positive neutrophils show high stimulated motility in vitro.

Chemotaxis, chemokinesis, and spontaneous locomotion of polymorphonuclear leukocytes (PMNs) of yersinia arthritis (YA) patients and healthy subjects with or without HLA-B27 were studied by agarose assay and membrane filter technique. HLA-B27 positive healthy control subjects and yersinia patients showed significantly higher response to chemotactic stimulus than HLA-B27 negative controls. Consequently, the high response was associated with HLA-B27 irrespective of YA. The high responder PMNs may contribute to the more severe inflammatory symptoms in YA patients with HLA-B27.

Rheumatic fever and its sequels in children. A follow-up study with HLA analysis.

An analysis of 170 attacks (in 158 children) treated with a diagnosis of rheumatic fever (RF) in 1956-1961 or 1970-1974 showed that the Jones revised criteria of RF were fulfilled in about 1/2 of the attacks. Arthritis occurred in 72%, carditis in 39%, chorea in 18%, and erythema marginatum in 1% of the attacks with confirmed diagnosis. No chorea was observed in 1970-1974. Follow-up of the patients showed favorable prognosis and low frequency of recurrences of RF. HLA analysis showed frequencies of A and B loci were similar, whereas "blank" finding in locus C was rarer in RF patients than in controls.

Ocular inflammation in Reiter's disease after Salmonella enteritis.

We studied characteristics of ocular inflammation in Reiter's disease after Salmonella enteritis in eight patients. After an acute onset with diarrhea, fever in six patients, and headache in three patients, all patients developed arthritis; six patients had myalgia; six patients, urethritis; and one patient, carditis. Sacroiliitis was found in four patients. All patients had HLA-B28 antigen. Conjunctivitis occurred in seven patients. It was mostly mild with no chemosis, follicles, or keratitis, and resolved in ten days. In one case palpebral edema, chemosis in the conjunctiva, and purulent exudate were seen. One patient had transient episodes of keratitis and corneal erosion for two months and episodes of conjunctivitis for 11 months. Three patients developed unilateral acute anterior uveitis with aqueous flare, cells, fine keratic precipitates, and fibrinous exudation from three to four years after the onset of the illness. One of these patients had vitritis and macular and papillary edema.

Leucocyte motility in the newborn: determination of spontaneous movement is essential in the in vitro assessment of neutrophil chemotaxis.

Polymorphonuclear leucocytes (PMNs) of the newborn show poor movement in vitro toward a chemotactic stimulus, such as zymosan-activated human serum (ZAS). This may result from a defect either in spontaneous movement or in the response of the cells to the stimulus. To identify the defect we studied chemotaxis, chemokinesis and spontaneous movement of cord blood PMNs by agarose assay and by the leading front modification of the Boyden chamber technique. Under agarose, cord PMNs showed much spontaneous movement. This, associated with poor stimulated movement, indicated a defect in the responsiveness of cord PMNs to ZAS. In the membrane filter, cord PMNs migrated spontaneously, and in the presence of ZAS, significantly less than adult cells. The weak spontaneous movement most probably resulted from poor deformability of cord PMNs and contributed to the weak stimulated movement of these cells in the filter. Our results indicate that the impaired chemotaxis was due to a defect in both responsiveness and deformability of cord PMNs rather than to a defect in their intrinsic ability to move.

Ocular inflammation associated with Yersinia infection.

We studied characteristics of ocular inflammation associated with Yersinia infection in 23 patients. After an acute onset with fever, diarrhea, and abdominal pain, 22 patients developed arthritis, 11 patients developed myalgia, 11 patients developed Reiter's syndrome, 17 patients developed acute anterior uveitis, and nine patients developed conjunctivitis. Sacroiliitis was found in 12 patients. The patients had high erythrocyte sedimentation rates, leukocytosis, and lack of antinuclear antibodies and rheumatoid factor. All 17 patients tested had HLA-B27 antigen. The patients with acute anterior uveitis showed aqueous flare, cells, fine keratic precipitates, and often exudates, posterior synechiae, vitritis, and macular edema. Acute anterior uveitis was mostly unilateral and resolved during corticosteroids on the average during the first six weeks; recurrences were seen in about half of the cases. Conjunctivitis was generally mild with no chemosis, follicles, or keratitis; and it resolved in one week without treatment. Our results indicate that in HLA-B27 positive patients infective agents can trigger acute anterior uveitis or conjunctivitis, which often occur together with rheumatic diseases.

Impaired neutrophil chemotaxis in Pelger-Huët anomaly.

A family has previously been described in which four members with Pelger-Huët (P-H) anomaly suffered from recurrent attacks of abdominal pain and fever, while one member, whose polymorphonuclear leucocytes (PMNs) were also hyposegmented, was asymptomatic. We studied chemotaxis, chemokinesis and spontaneous locomotion of PMNs in the three surviving symptomatic sisters, in their asymptomatic brother and in two asymptomatic members of another family with P-H anomaly. The spontaneous migration of the PMNs of the three sisters was significantly slower both under agarose and in a membrane filter than that of the PMNs of the asymptomatic patients with P-H anomaly. Chemotactic and chemokinetic locomotion of the PMNs of the symptomatic sisters was also slow. Our results suggests that the impaired chemotaxis was due to a defect in the intrinsic locomotor capacity of PMNs rather than in their deformability or their responsiveness to the chemotactic stimulus.