Inflammatory bowel disease associated circulating immune complexes

Circulating immune complexes have been detected in patients with inflammatory bowel disease (IBD). To determine if these complexes are related specificially to IBD or more generally to loss of intestinal mucosal integrity, we compared circulating immune complex levels in the sera of 86 IBD patients, nine pseudomembranous and nine bacterial colitis patients, and 42 healthy controls. Immune complexes were measured by a Raji cell radioimmunoassay. Raji detectable circulating immune complex levels were significantly higher in the IBD group than in the healthy controls (P<0·001). Circulating immune complex levels in the pseudomembranous-bacterial colitis group and the healthy controls were essentially identical. While nearly 20% of the IBD patients (16 of 86) had abnormally high levels, none of the patients with the other forms of intestinal inflammation (0 of 18) had abnormal levels. These data suggest that the circulating immune complexes present in inflammatory bowel disease patients are related to the IBD process rather than to non-specific mucosal cell (barrier) damage. Patients with intestinal inflammation and normal peripheral immune complex levels also had normal mesenteric vein levels. These data suggest that lack of formation, rather than more efficient hepatic reticuloendothelial clearance, was primarily responsible for the absence of detectable complexes in Raji negative individuals. Circulating immune complex levels did not correlate with type, location, severity, or extraintestinal manifestations of inflammatory bowel disease. The absence of Raji detectable circulating immune complexes in the majority of patients, even in those with extraintestinal manifestations, raises serious doubts about the pathogenic significance of such complexes. Nevertheless, as the circulating immune complexes appear to be disease related, they may be used to isolate and identify disease specific antigen(s) of possible aetiological importance.     

Cutaneous vasculitis and IgA glomerulonephritis in ankylosing spondylitis.

Two patients with ankylosing spondylitis were found to have IgA nephropathy and leucocytoclastic cutaneous vasculitis. Immunofluorescence showed perivascular deposition of IgA in the skin of one patient and in the mesangium of both patients. Such an association has been reported only once before. This supports the concept of abnormal IgA immune stimulation in the pathogenesis of ankylosing spondylitis.     

Inflammatory bowel disease in ankylosing spondylitis

Routine detailed gastroenterological investigations were performed in a series of 47 ankylosing spondylitics. Evidence of chronic inflammatory bowel disease was found in eight patients, a prevalence of 17%. Unsuspected bowel disease was found in the absence of symptoms in three of these patients.     

Relation of microscopic haematuria in ankylosing spondylitis to circulating IgA containing immune complexes.

Ankylosing spondylitis (AS) is associated with IgA nephropathy. To study the pathogenetic mechanism of this association the presence of haematuria and circulating IgA containing immune complexes (IgA ICs) in 70 patients with AS was determined. In this retrospective study haematuria was present in 15 patients and 25 patients had IgA ICs. Circulating IgA ICs were shown in 9/15 (60%) of the patients with haematuria and in 16/55 (29%) of those without haematuria. These results suggest that IgA ICs in patients with ankylosing spondylitis have a pathogenetic role in causing IgA nephropathy.     

The absence of circulating immune complexes in patients with ankylosing spondylitis

Summary Sera from 50 patients with well-defined ankylosing spondylitis were examined for circulating immune complexes using both a C1q binding (fluid phase) assay and a Raji cell assay. No more than five of the patients assessed had circulating immune complexes by either one of these techniques and none were positive in both. This result is in contrast to the high prevalence in sera from unselected patients with rheumatoid arthritis and systemic lupus used as positive controls.     

强直性脊柱炎相关IgA肾病临床与病理特征

目的：回顾性分析强直性脊柱炎伴IgA肾病的临床病理特点.方法：15例（男12例,女3例）强直性脊柱炎患者,临床有肾脏损害表现,肾活检光镜以系膜增生性病变伴或不伴新月体形成,免疫荧光检查以IgA系膜区沉积为主,回顾分析其临床及病理特征.结果：发生肾损害时强直性脊柱炎病史平均为49.7月（1～240月）,5例患者诊断肾病后才确诊有强直性脊柱炎.13例患者（86.7%）HLA-B27阳性.7例（46.7%）肾损害表现为尿检异常,临床有蛋白尿和镜下血尿;2例（13.3%）以肉眼血尿起病,表现为急性肾炎综合征;6例（40%）起病时表现为慢性肾功能不全.肾活检病理,所有患者均有肾小球系膜和基质增生性病变,8例患者（53.3%）有新月体形成,2例（13.3%）可见节段袢坏死.4例（26.7%）有间质小血管纤维素样坏死,6例（40%）见血管透明变性,3例（20%）间质血管有小血栓形成.10例（66.7%）患者有不同程度的肾小球废弃,4例（26.7%）有半数以上肾小球废弃.8例（53.3%）小管间质中重度纤维化.间质CD68阳性细胞浸润均数为394（188～764）个/mm2.结论：强直性脊柱炎肾脏损害并不少见,临床症状隐匿,容易误诊或漏诊.其肾脏病理改变中突出的血管病变,提示其发病机制不同于原发性IgA肾病,而是继发于强直性脊柱炎.     

IgA containing immune complexes and hematuria in ankylosing spondylitis. A prospective longitudinal study

The occurrence of circulating immune complexes containing IgA (IgA-IC) was studied in groups of patients with ankylosing spondylitis (AS) selected for the presence or absence of hematuria. In studies done with 4 kinds of assays, IgA-IC were found more frequently and in higher titers in the 18 patients with AS with hematuria than in the 40 patients with AS without hematuria. Comparison of clinical indices of disease activity in these patient groups showed that the disease was more active in patients with AS with hematuria. Our findings confirm those made in a previous retrospective study on the relation between hematuria and circulating IgA-IC in AS and suggest that circulating IgA-IC play a role in the pathogenesis of hematuria in AS.     

Circulating immune complexes in patients with ankylosing spondylitis.

EDTA plasma samples from 13 patients with ankylosing spondylitis (AS) were fractionated on Sephadex G-200 and the quantities of C3 and IgG within the first protein peak determined by a sensitive haemagglutination-inhibition assay. Seven patients with AS had G3 detectable in the first peak and this was associated with an increased concentration of IgG in the corresponding fraction. These 7 patients had more active disease but did not have more peripheral arthritis. Our results indicate that circulating immune complexes capable of initiating complement activation are present in the circulation of patients with ankylosing spondylitis.     

Histoplasmosis. Association with circulating immune complexes, eosinophilia, and mesangiopathic glomerulonephritis.

A patient with disseminated histoplasmosis, eosinophilia, and transient mesangiopathic glomerulonephritis stimulated a search for the presence of circulating immune complexes. Serum samples obtained on the fifth and 11th hospital days were strongly positive for ciculating immune complexes by both the Raji cell radioassay and the C1q solid phase assay. During the course of complete clinical recovery without therapy, both assays were weakly positive for circulating immune complexes on day 33. On day 56 they were negative. Using this case as a prototype, possible mechanisms for the renal immunopathology and the eosinophilic response are discussed with reference to the immunological perturbations thay may be observed in systemic mycotic infection.     

Milk precipitins, circulating immune complexes, and IgA deficiency.

Twenty-two patients with selective IgA deficiency were studied for the presence of serum precipitins to bovine milk, bovine and fetal calf serum, and circulating immune complexes. Fifty-nine percent had circulating immune complexes, 50% had milk precipitins, 23% had precipitins to bovine serum, and 13% had precipitins to fetal calf serum. All patients with precipitating antibodies against milk or against bovine or fetal calf serum had circulating immune complexes and the precipitin titers correlated with the amount of circulating immune complexes. After one IgA-deficient patient had drunk 100 ml of milk, studies of sequential serum samples showed the presence of casein in the circulation at 60 min and the appearance of increasing amounts of immune complexes for 120 min. These findings are interpreted to indicated that in human beings the IgA system may provide a major barrier to absorption of immunogens from the gastrointestinal tract.     

Secretory IgA: immune defence pattern in ankylosing spondylitis and klebsiella.

Saliva secretory IgA (sIgA), secretory component (SC); serum immunoglobulins (IgG, IgA, IgM), complement (C3, C4), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were performed in 32 patients with ankylosing spondylitis and 29 normal controls. They were investigated for carriage in the faeces of Klebsiella spp. on 3 occasions over the previous months. Throat swabs and urine were cultured at the same time as immunological estimations were done. 24-hour urine sIgA specimens were studied in 13 patients and 12 normal controls. Significantly raised mean values of saliva sIgA and serum IgG, IgA, C3, and C4 were found in patients with raised values of serum ESR and CRP levels when correlated with controls. Raised values of sIgA in saliva, which is an important factor of the local immune defence mechanism of mucosal surfaces, suggests the presence of an antigenic stimulus from the gastrointestinal system in ankylosing spondylitis during activity of disease.     

IgA containing immune complexes in rheumatoid vasculitis and in active rheumatoid disease

Serum and synovial fluid (SF) from 68 patients with rheumatoid arthritis (RA) were studied for the presence of immune complexes (IC) and the results correlated with extraarticular features and/or disease activity. IC were measured by the 125I Clq binding assay (ClqBA) and with one detecting IgG, IgA, C3 or C4 in IC. Disease activity correlated significantly with IgG or IgA containing and Clq binding IC. The IgA containing IC were found only in 25% of the patients, including all but one case of rheumatoid vasculitis, but otherwise only in seropositive active RA. C3 and C4 IC did not correlated with disease activity, seropositivity or vasculitis. IC in serum did not correlate with SF levels, but C4 containing IC were more frequent in SF (60%) than in serum (30%). Thus serum IC did not reflect SF levels. Patients with vasculitis showed more IC in the sera than in SF.     

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.     

Analysis of circulating immune complexes from patients with ankylosing spondylitis by gel electrophoresis and immunoblotting using antiserum against a psoriasis associated retrovirus-like particle.

Circulating immune complexes (CIC) were isolated from patients with ankylosing spondylitis (AS) and healthy blood donors by isopycnic ultracentrifugation in sucrose gradients. The CIC were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The major components of the CIC were identified as albumin, immunoglobulins, and complement factors. A 70 kD component and several low molecular weight components (Mr 19 kD and 14 kD (doublet] were detectable only in CIC from patients with AS. An antiserum raised against the envelope glycoprotein, gp70, of a psoriasis associated retrovirus-like particle was applied to check for cross reacting activity. This antiserum reacted with both a 70 kD and a 40-45 kD component in CIC from three out of six patients but not with CIC from any of the blood donors.     

Ankylosing spondylitis and inflammatory bowel disease. I. Prevalence of inflammatory bowel disease in patients suffering from ankylosing spondylitis.

To establish the prevalence of inflammatory bowel disease in ankylosing spondylitis (AS), 79 AS patients underwent detailed medical screening, including sigmoidoscopic and roentgenological examination, 48 had gastrointestinal symptoms and the others did not. In 3 patients a diagnosis of Crohn's disease was made which was previously established. In all other patients inflammatory bowel disease could be excluded. The prevalence of inflammatory bowel disease in this series of patients with AS therefore was 3.8%.