High levels of antipeptidoglycan antibodies in psoriatic and other seronegative arthritides

Bacterial cell wall peptidoglycan, the arthritogenic factor in adjuvant induced arthritis, may also be involved in the etiology of some human rheumatic diseases. Patients with some seronegative rheumatic diseases like ankylosing spondylitis and Reiter's syndrome have elevated antibody titers to peptidoglycan. Using an ELISA with soluble peptidoglycan, we examined the sera of 110 patients with psoriatic arthritis, psoriasis without arthritis and a variety of other joint diseases. Antibody titers were significantly higher (p less than 0.001) among the 22 patients with psoriatic arthritis than the 16 patients with psoriasis without arthritis. Patients with other seronegative arthritides also had higher levels of antipeptidoglycan antibodies than patients with rheumatoid (seropositive) arthritis, osteoarthritis and crystal induced arthritis. Our results furnish additional support for the suggestion for a bacterial role in the pathogenesis of psoriatic and some other seronegative arthritides.     

Human immunodeficiency virus-associated psoriasis, psoriatic arthritis, and Reiter's syndrome: a disease continuum?

The presence of peripheral arthritis and HLA-A, B, C, DR, and DQ antigens was evaluated prospectively in 18 Caucasian men with human immunodeficiency virus-associated psoriasis. An asymmetric polyarthritis occurred in 32% of the patients and correlated with the presence of HLA-B27. Extensive clinical overlap between psoriatic arthritis, psoriasis, and Reiter's syndrome was noted. No significant excess of the HLA antigens previously found to be associated with psoriasis was seen, which suggests that human immunodeficiency virus-associated psoriasis per se may instead constitute another form of spondylarthropathy that is more closely related to Reiter's syndrome.     

Antibodies to cytoplasmic intermediate filaments in rheumatic diseases

Antibodies to 2 types of cytoplasmic intermediate filaments (IMF)--vimentin and cytokeratin filaments--were assayed in sera from various rheumatic diseases by indirect immunofluorescence using cultured human embryonic fibroblasts and an epithelial cell line, PtK 2, as substrates. These antibodies belonged mainly to the IgM class and were detected in most of the sera. Vimentin filament antibodies of IgG or IgA class were frequent in Sj?gren's syndrome (43%). Antibodies to another type of IMF, cytokeratin filaments, were also more prevalent in Sj?gren's syndrome (64%) than in systemic lupus erythematosus (50%), rheumatoid arthritis (46%) and other hospital patients (8%). Our results show that intermediate filaments are a major target for autoantibodies in rheumatic diseases, especially in Sj?gren's syndrome. The presence of intermediate filament IgA antibodies suggest that the stimulus for their production lies at epithelial surfaces.     

Antinuclear antibodies in ankylosing spondylitis, psoriatic arthritis, and psoriasis.

Granulocyte-specific antinuclear antibodies (GS-ANA) were detected in the sera of 5 of 88 patients with ankylosing spondylitis (AS) and in 7 of 52 cases of psoriatic arthritis (PsA), but were not found in 91 patients with malignant or non-malignant chest disease nor in 25 cases of psoriasis. Organ non-specific ANA were present in serum from 6 cases of AS and 1 of PsA. None of the sera gave significant levels for soluble immune complexes as detected by a C1q-binding assay. The presence of antinuclear antibodies was not associated with clinical features or drug therapy in either AS or PsA.     

Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases

Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n = 268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and mycobacterial 65K antigens), hsp73, and hsp90. Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n = 36) and from patients with rheumatoid arthritis, Sj?gren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupus erythematosus, and systemic sclerosis. Autoantibodies to hsp60 were relatively more common (greater than or equal to 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquisita, and bullous pemphigoid. Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients with Lyme disease and ulcerative colitis. Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein autoreactivity develops. However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupus erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders.     

Psoriasis and psoriatic arthritis associated with human immunodeficiency virus infection

It has been well established that psoriasis, psoriatic arthritis, and Reiter's syndrome can occur in patients with HIV infection. These arthocutaneous diseases tend to occur in temporal proximity to the development of AIDS and ARC, and their clinical manifestations are unusually severe. The appearance or exacerbation of psoriasis, arthritis, or Reiter's syndrome in a high-risk person should alert the clinician to possible underlying HIV infection. Treatment should be dictated by the severity of the skin and musculoskeletal disease as well as by the status of the immune system. Zidovudine appears to be effective in many diseases, especially psoriasis, and nonsteroidal antiinflammatory drugs are the mainstay for arthritis. Immunosuppressive agents such as methotrexate and azathioprine are contraindicated because they exacerbate immunodeficiency and promote infections. Epidemiologic studies suggest that the prevalence of these diseases, especially Reiter's syndrome, may be higher in HIV-positive populations than previously thought, especially in those patients with AIDS and ARC. Immunogenetic factors like HLA-B27 are important in the predisposition to Reiter's syndrome associated with HIV infection; however, it is not clear what role they play in HIV-associated psoriasis. Mechanisms underlying these observations remain unclear, although potential insights into the pathogeneses of psoriasis and Reiter's syndrome may be gained through future studies. Already it seems likely that CD4-positive helper T-cells, the target of HIV, are not necessary for the expression of psoriasis or Reiter's syndrome, and because of HLA class I associations, a role for CD8 positive cytotoxic T lymphocytes can be suspected. Infections, promoted by the profound immunodeficiency of AIDS, seem to be the most plausible explanations for the cutaneous and articular complications of HIV infection.     

Increased levels of IgA antibodies to cytokeratin-18 and epidermal keratin in rheumatoid arthritis

Objective. To investigate whether levels of antibodies to cytokeratin-18 (CK-18) and epidermal keratin (EPK) were raised in patients with rheumatoid arthritis (RA). Methods. We measured antibodies to CK-18 and EPK in patients with RA and in patients with osteoarthritis (OA), as well as in normal control subjects by means of an enzyme-linked immunosorbent assay. Results. IgA antibodies to both CK-18 and EPK were significantly increased in patients with RA compared with the controls and with patients with OA (P < 0.0001). No difference was noted in the levels of IgG or IgM antibodies to CK-18 or EPK between controls and patients with OA or RA. Conclusion. Raised levels of IgA autoantibody to CK-18 and EPK may reflect damage to cytokeratin-containing cells (e.g., in synovial endothelium) and could be a useful disease marker in RA.     

Anti-MAM antibodies in rheumatic disease: evidence for a MAM-like superantigen in rheumatoid arthritis?

OBJECTIVE: Superantigens (SAg) are potent immunomodulatory microbial proteins that can activate T cells, B cells, natural killer cells, and monocytes and are known to trigger experimental autoimmune disease. We investigated whether sera from patients with rheumatic diseases contained elevated antibodies to Mycoplasma arthritidis mitogen (MAM) or staphylococcal enterotoxins A and B (SEA and SEB). METHODS: Standard ELISA were used to measure IgG responses to SAg and IgM and IgG rheumatoid factors and total IgM and IgG levels. Modifications of standard lymphocyte proliferation assays were used to determine functional consequences of the observed antibodies. Results: Antibodies to MAM were elevated in sera from patients with rheumatoid arthritis (RA) compared to sera from patients with systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, or healthy controls. Responses to other SAg were also elevated in rheumatic disease sera, but the levels were not specific for a given rheumatic disease. Anti-superantigen antibody levels did not correlate with the presence of rheumatoid factor. CONCLUSION: The selected elevation of antibodies to MAM in RA sera suggests that MAM or a MAM-like molecule might be associated with RA, whereas elevation of antibodies to SEA and SEB in sera from patients with rheumatic diseases was less specific.     

Antibodies to tissue transglutaminase and Saccharomyces cerevisiae in ankylosing spondylitis and psoriatic arthritis

OBJECTIVE: Subclinical gut inflammation has been described in patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Joint involvement has also been reported related to celiac disease. We investigated IgA antibodies to bovine tissue tranglutaminase (tTg) and IgA and IgG antibodies to human tTg and to Saccharomyces cerevisiae (ASCA) in patients with AS and PsA. METHODS: We evaluated the frequency of IgA antibodies to bovine tTg, and of IgA and IgG antibodies to human tTg and to ASCA in 43 patients with AS and 75 with PsA. As control groups we considered 79 patients with rheumatoid arthritis (RA) and 78 healthy blood donors. RESULTS: We detected antibodies as follows: IgA antibodies to bovine tTg in 1/43 patients with AS, 3/75 with PsA, 1/79 with RA, and in 9/78 healthy controls; IgA antibodies to human tTg in 1/43 patients with AS, 1/75 with PsA, 1/79 with RA, and in 3/78 healthy controls; IgG antibodies to human tTg in 1/43 patients with AS, 4/75 with PsA, 5/79 with RA, and in 7/78 healthy controls. IgA ASCA were confirmed in 10/43 patients with AS, 7/75 with PsA, 14/79 with RA, and in 7/78 healthy controls; IgG ASCA were present in 5/43 patients with AS, 4/75 with PsA, 8/79 with RA, and in 8/78 healthy controls. No statistically significant difference was observed in the prevalence of IgA or IgG antibodies to bovine and human tTg and in the frequency and in mean level of IgA or IgG ASCA between the studied groups or between each group and healthy controls. CONCLUSION: Our data fail to show an increased prevalence of autoantibodies associated with celiac and Crohn's disease in patients with AS and PsA.     

Anti-saccharomyces cerevisiae IgA antibodies are raised in ankylosing spondylitis and undifferentiated spondyloarthropathy

OBJECTIVES: To investigate whether anti-Saccharomyces cerevisiae antibodies (ASCA), a marker for Crohn's disease (CD), are present in spondyloarthropathies (SpA) and in the subgroups ankylosing spondylitis (AS), undifferentiated SpA (uSpA), and psoriatic arthritis (PsA), in comparison with healthy and inflammatory controls (patients with rheumatoid arthritis (RA)). METHODS: ASCA IgA and IgG levels were measured with an enzyme linked immunosorbent assay (ELISA) kit (Medipan, Germany) in 26 patients with CD, 108 patients with SpA (43 patients with AS, 20 patients with uSpA, 45 patients with PsA), 56 patients with RA and 45 healthy controls. Gut biopsy samples were available in 18 AS and 10 patients with uSpA, these samples were screened for the presence of inflammation. RESULTS: Both ASCA IgG and IgA levels were raised in CD compared with healthy controls and patients with RA. ASCA IgA, but not IgG levels, were higher in SpA than in both healthy and RA controls. ASCA IgA levels were raised in AS and uSpA, but not in PsA. No significant differences in ASCA IgA levels were noted between patients with SpA with and without histological gut inflammation. CONCLUSION: ASCA IgA levels are significantly higher in SpA, and more specifically in AS, than in healthy controls and patients with RA. This is the first serum marker associated with SpA. No correlation between the presence of subclinical bowel inflammation and ASCA IgA levels was noted. However, it remains to be evaluated whether patients with SpA with ASCA have an increased risk of developing CD.     

Postsalmonella reactive phenomena in 2 patients with ankylosing spondylitis: no modification of the underlying disease

HLA-B27 related disease occurs in 2 main forms, ankylosing spondylitis (AS) or reactive arthropathy/Reiter's syndrome. These entities often "breed true" within families or distinct ethnic groups. Reactive arthropathy/Reiter's syndrome may be complicated by AS, but little is known about the impact on AS of a de novo reactive arthropathy occurring at a later date. We describe 2 patients with AS who developed postsalmonella reactive phenomena several years after the onset of their primary disease. In both patients the intestinal salmonella infection did not modify the course of the AS.     

IgA and IgG autoantibodies against alpha-fodrin as markers for Sjögren's syndrome. Systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of IgA and IgG autoantibodies against alpha-fodrin in patients with primary and secondary Sj?gren's syndrome (SS) and controls. METHODS: An ELISA detecting IgA and IgG antibodies against alpha-fodrin was developed. We examined the prevalence of IgA and IgG antibodies against alpha-fodrin in patients with primary and secondary SS, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and blood donors. RESULTS: IgA antibodies against alpha-fodrin were detected in 64% of patients with primary SS (n = 85), 47% of patients with secondary SS and SLE (n = 15), and 86% of patients with secondary SS and RA (n = 7). IgA autoantibodies against alpha-fodrin were detected in only one of 160 sera obtained from blood donors and in one of 50 and 2 of 12 sera obtained from SLE and RA patients without sicca syndrome, respectively. The prevalence of IgG antibodies against alpha-fodrin in SS was lower: they were detected in 55% of sera obtained from patients with primary SS, 40% of patients with secondary SS and SLE, and in 43% of patients with secondary SS and RA. Three of 160 sera from blood donors and one of 50 and 5 of 12 sera from SLE and RA patients without sicca syndrome, respectively, contained IgG antibodies against alpha-fodrin. CONCLUSION: IgA rather than IgG antibodies against alpha-fodrin are specific for and frequently observed in primary and secondary SS and are useful markers for this autoimmune disorder.     

Rheumatoid factors in psoriatic arthropathy and in Waaler-Rose negative rheumatoid arthritis

Summary Serum levels of IgG, IgA and IgM rheumatoid factor (IgG RF, IgA RF and IgM RF) were determined by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in 42 Waaler-Rose negative patients with psoriatic arthropathy (PsA) type 1 (arthritis with involvement of distal interphalangeal joints) and type 3 (polyarthritis of rheumatoid type) according to the criteria of Moll and Wright as well as in 53 patients with Waaler-Rose negative rheumatoid arthritis (RA). Elevated levels of RF were found in 22% of patients with PsA type 3 and 45% of patients with Waaler-Rose negative RA. In contrast, none of the patients with PsA type 1 had detectable amounts of RF. It is suggested that the presence of IgG, IgA or IgM RF in patients having psoriasis in conjunction with inflammatory polyarthritis indicates the RA nature of the joint disease and should be considered as exclusion criterion for the diagnosis of PsA.     

IgA antibodies to Klebsiella pneumoniae in ankylosing spondylitis

Serum IgA antibodies to Klebsiella pneumoniae were measured in 65 patients with ankylosing spondylitis (AS) during different phases of disease activity and compared with the antibody level in 21 psoriatic arthritis (PsA) patients, 43 rheumatoid arthritis (RA) patients and 57 healthy controls. The mean IgA antibody to Klebsiella in AS patients with an erythrocyte sedimentation rate (ESR) greater than or equal to 15 mm/h was significantly higher than the antibody level in patients with an ESR less than 15 mm/h (p less than 0.02) and tended to increase with rising ESR. There was a significant difference in anti-Klebsiella antibody levels between AS patients with an elevated ESR and antibody levels in PsA patients (p less than 0.001), RA patients (p less than 0.001) and healthy controls (p less than 0.005). There was no difference between healthy controls and patients with PsA, RA or AS patients with a low ESR. The IgA anti-Klebsiella antibody was specifically absorbed out from sera with inactivated klebsiella pneumoniae organisms. Antibody levels to Candida albicans and Escherichia coli did not differ in patients vis-à-vis control subjects. The mean serum anti-Klebsiella IgA level was found to be higher in patients who were either clinically active or had positive faeval cultures, when compared with patients with inactive disease and negative cultures, but these differences were not statistically significant, although when both parameters were examined together a significant additive effect was detected (p less than 0.001). It is concluded that patient with AS exhibit a specific elevation of serum IgA antibody to Klebsiella antigen.     

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, acral necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE. Received: 12 April 1998 / Accepted: 24 April 1998     

Arthropathy associated with palmoplantar pustulosis

Summary A survey of 170 patients with a diagnosis of palmoplantar pustulosis (PPP) has been undertaken. Detailed family histories of our patients were compiled, dermatological and rheumatological examinations were made. Radiography was performed in patients with clinical suspicions of spinal and/or sacroiliacal, sternoclavicular and sternocostal joint involvement. Active chest-wall symptoms were screened by scintigraphy. Twenty-five patients (16 females, 9 males, with an age range of 32–66, mean 51 years) had some rheumatic complaints. Fifteen of them (60%) had anterior chest-wall involvement, 6 (24%) sacroiliitis (3 of whom also had AS) and 11 (44%) peripheral arthropathy. Six other patients suffered from transient and migratory joint pain. The joint disease was mild in all but 6 cases. Laboratory tests showed increased ESR in 6 patients (24%); only 3 of these patients had elevated CRP. A slightly elevated haptoglobin and/or orosomucoid were found in 12 cases (48%). Elevated IgA was present in 4, IgG in 2 and IgM in 1 patient. Fungal and bacteriological cultures of the skin were negative. A family history of psoriasis was present in 4 patients (16%), of psoriatic arthropathy in 1 patients (4%) and of PPP in 2 patients (8%). Six patients (24%) had concomitant psoriasis. No association between PPP H1a-AC antigens was found. A high incidence of HLA-B27 antigen, present in 8 patients (32%), was documented. A similar association with HLA-B27 has been found in patients with psoriatic arthritis (16). The feeble association with HLA-B13,-17,-37 and CW6 found in psoriasis was not present. The findings show immuno-genetic and clinical similarities between arthropathy associated with PPP and psoriasis and support the view that there is an association between the two diseases.     

Rheumatic manifestations of human immunodeficiency virus infection

PURPOSE: The prevalence and characteristics of the rheumatic and extra-rheumatic manifestations of human immunodeficiency virus (HIV) infection were determined in a prospective manner. PATIENTS AND METHODS: One hundred one patients with HIV infection were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS: The musculoskeletal system was involved in 72 patients. Thirty-five patients had arthralgias, 10 had Reiter's syndrome, two had psoriatic arthritis, two had myositis, and one had vasculitis. Also found were two previously unreported syndromes. The first, occurring in 10 patients, consisted of severe intermittent pain involving less than four joints, without evidence of synovitis, of short duration (two to 24 hours), and requiring therapy (ranging from nonsteroidal antiinflammatory drugs to narcotics). The second, occurring in 12 patients, consisted of arthritis (oligoarticular in six patients, monoarticular in three patients, and polyarticular in three patients) involving the lower extremities and lasting from one week to six months. The synovial fluid of five patients (three with arthritis, one with Reiter's syndrome, and one with psoriatic arthritis) was sterile and inflammatory. CONCLUSION: Musculoskeletal complications are common in advanced stages of HIV infection. Persons in a high-risk group for HIV infection who manifest oligoarthritis with or without any other extra-articular manifestation suggestive of Reiter's syndrome or other form of spondyloarthropathy should be tested for HIV.     

Immunological variables and acute-phase reactants in patients with ankylosing spondylitis (Bechterew's syndrome) and their relatives

Summary Serum and EDTA blood from 120 patients with ankylosing spondylitis (Bechterew's syndrome) and serum from 138 first-degree relatives of patients and from 42 adult blood donors were investigated. Increased serum concentrations of IgA and IgG and complement factors C3 and C4 were found in total groups of HLA B27-positive male or female patients compared with controls or relatives. The men had higher serum concentration of IgA and complement factors than the women, whereas IgM concentration was higher in the women. These patterns were found in controls, in relatives and in patients. Increased concentrations of IgA and of C4 were characteristic of all patients whereas IgG and IgM and C3 concentrations were likewise elevated in patients with peripheral joint arthritis/arthropathy. Increased levels of circulating immune complexes (CIC) were associated with peripheral joint arthritis and were strongly correlated with IgG or CRP concentrations in serum. Total haemolytic complement activity in serum was negatively correlated with concentrations of CIC or CRP indicating complement activation in patients with such complexes. No differences in serum concentrations of Ig or complement factor concentrations were seen between HLA B27-positive and negative relatives with normal sacro-iliac joints or between relatives and controls. Strong mutual correlations were seen among IgG, IgM, complement factors, CRP, SAA, sedimentation rate and alpha₂-macroglobulin. When the present findings were combined with our previous results it turned out that AS, and psoriasis with or without arthropathy, and acute anterior uveitis (AAU) in combination with sacro-iliitis, may be described as IgA-related conditions and that increased serum C4 was related to sacro-iliitis in all these disorders.     

Psoriatic arthritis with ANCA‐positive vasculitis: a rare association

Psoriatic arthritis is an inflammatory arthropathy in patients with psoriasis. Although 8% of patients affected with psoriasis without vasculitic manifestations are positive for perinuclear antineutrophilic cytoplasmic antibody (P‐ANCA), cutaneous vasculitis in psoriatic arthritis with a positive P‐ANCA is rare. We report a case of a 46‐year‐old‐man with a 25‐year history of plaque psoriasis admitted with joint pain and rash. He was subsequently diagnosed as having psoriatic arthritis and leucocytoclastic vasculitis with positive ANCA and was treated with methotrexate and corticosteroids. We hereby highlight the association of vasculitis with positive ANCA in a patient with psoriatic arthritis.     

Arthritis in the acquired immunodeficiency syndrome and other viral infections.

Musculoskeletal conditions occurring in individuals with human immunodeficiency virus infection are becoming increasingly well documented. Arthritis with features of Reiter's syndrome or psoriatic arthritis has been further studied; an association with HLA-B27 but not with HLA antigens chemically associated with psoriasis or psoriatic arthritis has been demonstrated. Human immunodeficiency virus has been identified in synovial fluid dendritic cells and in the synovium; immunohistochemical analysis is revealing the nature of the lymphocyte infiltrate in the synovium of affected individuals. Postmortem studies suggest that there may be histologic evidence of premature aging in clinically unaffected joints from patients with acquired immunodeficiency syndrome. Epidemiologic studies are needed to elucidate which rheumatic lesions occur as a direct consequence of human immunodeficiency infection and which may be chance associations.