Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis.

Kanerud, L; Engström, Gunilla Norhagen; Tarkowski, Andrej

doi:10.1136/ard.54.4.256

Cited by 15 publications

(14 citation statements)

References 55 publications

(30 reference statements)

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“…These percentages were based on studies in 350 adult RA patients. Other studies, which mention longitudinal evaluation of serum immunoglobulin levels, report a general decrease of immunoglobulin levels during SSZ treatment and development of hypogammaglobulinemia in only one other patient (3,17,19). Most studies on SSZ treatment in RA do not routinely evaluate levels of immunoglobulins (1,2,4,25); therefore cases of hypogammaglobulinemia or dysimmunoglobulinemia may have remained undetected (22,23).…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro activity of B cells measured as proliferation and immunoglobulin synthesis was inhibited by SSZ (29,30). In addition, SSZ has been shown to decrease serum levels of IL-6 in RA patients, and IL-6 is known as a potent B-cell growth and differentiation factor (19). It is suggested that SSZ inhibits IL-6 production and thereby downregulates B-cell differentiation and maturation (19).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, SSZ has been shown to decrease serum levels of IL-6 in RA patients, and IL-6 is known as a potent B-cell growth and differentiation factor (19). It is suggested that SSZ inhibits IL-6 production and thereby downregulates B-cell differentiation and maturation (19). In patients with RA, SSZ treatment reduces c/d lymphocytes in the duodenal mucosa, which may indicate an effect of SSZ on the gut immune system.…”

Section: Discussionmentioning

confidence: 99%

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Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis

Rossum

Fiselier

Franssen

et al. 2001

Scandinavian Journal of Rheumatology

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This article describes the effects of sulfasalazine (SSZ) treatment on serum immunoglobulin (Ig) levels in 6 children with oligoarticular- or polyarticular onset juvenile chronic arthritis (JCA). None of the children who developed dysimmunoglobulinemia during treatment showed clinical symptoms of this adverse event, in particular none developed severe infections. All patients regained normal immunoglobulin levels after discontinuing SSZ treatment. One patient with a partial IgA deficiency at the start of SSZ treatment showed a slow increase in the IgA level during treatment. During follow-up (4-6 years), one patient spontaneously developed a dysimmunoglobulinemia and one patient developed diabetes mellitus. Based on these case reports and review of the literature we advocate monitoring of serum immunoglobulin levels while on SSZ treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis

Rossum

Fiselier

Franssen

et al. 2001

Scandinavian Journal of Rheumatology

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“…Thus, the treatment period in the present study may have been too short to significantly decrease the jejunal perfusion fluid antibody concentrations. Moreover, it was recently shown that sulphasalazine excerts inhibitory effect only on systemic immunoglobulin production, whereas no effects on mucosal immunoglobulin production are observed 21. It is also possible that the clinical effect of sulphasalazine is mediated by other mechanisms than reduction of antibody production, for example by modifying cytokine or granulocyte protein release.…”

Section: Discussionmentioning

confidence: 99%

Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis

Mäki-Ikola

Hällgren

Kanerud

et al. 1997

Annals of the Rheumatic Diseases

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Objective-To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Methods-Antibodies against three diVerent Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay. Results-The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS. Conclusion-There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.

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“…IgA RF is produced in the mucosal compartments and is a marker of inflammation in or near mucosal membranes [34]. Sulfasalazine inhibits serum concentrations of IgA, IgG, IgA RF, and IgM RF [35]. It also decreases IL-6, a potent B cell differentiation factor closely involved in the regulation of IgA and IgG production.…”

Section: Gi Manifestations Of Ramentioning

confidence: 99%

Gastrointestinal and Hepatic Manifestations of Rheumatoid Arthritis

Ebert

Hagspiel

2011

Dig Dis Sci

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Rheumatoid arthritis (RA), characterized by inflammation of the synovium and surrounding structures, has a prevalence of 0.5-1%. Rheumatoid vasculitis (RV) is an inflammatory condition of the small- and medium-sized vessels that affects up to 5% of patients with RA with intestinal involvement in 10-38% of these cases. Clinically apparent RV of the gastrointestinal (GI) tract, while rare, is often catastrophic, resulting in ischemic ulcers and bowel infarction. Vasculitis of the colon may present as pancolitis clinically similar to ulcerative colitis. Rectal biopsies that include submucosal vessels are positive for vasculitis in up to 40% of cases. Abnormal esophageal motility in RA may result in heartburn and dysphagia. Chronic atrophic gastritis may be associated with hypergastrinemia and hypo- or achlorhydria, promoting small bowel bacterial overgrowth. RA is the most common cause of secondary amyloidosis with GI symptoms in 22% of affected patients. Although amyloid is usually found in the liver, it is rarely evident clinically. Felty's syndrome occurs in less than 1% of patients with RA and is characterized by neutropenia and splenomegaly. The liver may be involved with portal fibrosis or nodular regenerative hyperplasia. Liver histology is abnormal in 92% of RA patients at autopsy, although the changes are usually mild without associated hepatomegaly. Drug-induced liver disease may occur with aspirin, sulfasalazine, and methotrexate. Significant liver damage is rare if the drug is discontinued or the patient is properly monitored. RA can affect both the GI tract and the liver; changes are usually mild except with RV.

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Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis.

Cited by 15 publications

References 55 publications

Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis

Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis

Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis

Gastrointestinal and Hepatic Manifestations of Rheumatoid Arthritis

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