Elevated Rheumatoid Factor Research Articles

Rheumatoid factor in the serum of hepatitis C virus-infected patients: an increase in the titre during cold storage.

Storage of serum at 4 degrees C elevated the titre of rheumatoid factor (RF) as measured by nephelometry with IgG-coated latex in 12 of 38 specimens positive for hepatitis C virus. Increased RF following cold storage was not detected in HCV-negative sera. Most of the sera showing the cold-dependent elevation of RF had decreased complement hemolytic activity (CH50) after the cold storage. The RF titre elevated by cold storage decreased to the level of fresh serum by the addition of guinea pig serum as a complement supplement in a dose-dependent fashion. Thus, in the serum of some HCV-infected patients, the affinity of RF appears to be weak, and the binding between the RF and IgG coated on latex may be inhibited by the complement components of fresh serum.

Localized vasculitis of the gastrointestinal tract.

We studied the clinical and pathologic findings of 63 patients with localized vasculitis of the gastrointestinal tract, including 35 partial bowel resections, 14 cholecystectomies, five partial pancreatectomies, six appendectomies, one omentectomy, one gastrectomy, and one esophagectomy. Vasculitis was classified histologically as polyarteritis (n = 33), phlebitis (n = 12), Churg-Strauss angiitis (n = 8), small-vessel vasculitis (n = 6), Buerger's disease (n = 2), and giant-cell arteritis (n = 1). Nineteen of 33 cases of polyarteritis affected the small bowel or gallbladder, and nine patients with polyarteritis had elevated serum antinuclear antibodies or rheumatoid factor. Eight of 12 cases of phlebitis affected the right colon; there were giant cells in four of these 12 cases, a history of medication use in seven of eight cases, and no evidence of serum autoantibodies. Short-term follow-up (mean, 5 years) demonstrated that systemic disease developed in six of 23 patients with polyarteritis (four of whom had elevated serum rheumatoid factor or antinuclear antibodies), the patient with giant-cell arteritis, and one of two patients with Buerger's disease. Systemic vasculitis did not develop in patients with other types of vasculitis. We conclude that patients with gastrointestinal phlebitis, polyarteritis without serum autoantibodies, and small-vessel vasculitis have a low short-term risk for the development of systemic disease.

Selective increase of IgA rheumatoid factor in patients with gluten sensitivity.

An increased prevalence of raised autoantibodies, including rheumatoid factor, has been reported in patients with gluten sensitivity. However, rheumatoid factor has only been measured in small groups of patients and the findings have been conflicting. In this study IgM, IgG and IgA rheumatoid factor was measured in 89 patients with dermatitis herpetiformis and 22 patients with coeliac disease and compared with 89 normal controls. There was an increased prevalence of elevated IgA rheumatoid factor in the patients with dermatitis herpetiformis (13.5%; p = 0.036) and coeliac disease (18.2%; p = 0.078), while no such increase was found for the IgM or IgG rheumatoid factor isotypes. This selective increase of IgA rheumatoid factor suggests that rheumatoid factor production in patients with gluten sensitivity primarily results from immunological activation in the gut mucosa.

Reversible Magnetic Resonance Imaging Findings in metronidazole-induced Encephalopathy

Metronidazole, a 5-nitroimidazole widely used for treatment of trichomoniasis, giardiasis, amebiasis, and anaerobic infections, produces a number of neurologic side effects including peripheral neuropathy, encephalopathy, cerebellar dysfunction, and seizures [1-3]. We report brain MRI findings in a patient with metronidazole-induced sensory neuropathy, encephalopathy, and cerebellar dysfunction. To our knowledge there are no previous reports of brain MRI changes due to metronidazole toxicity. Case report. A 45-year-old Asian Indian woman who had been living in the United States for the past 10 years was hospitalized with complaints of confusion, gait unsteadiness, and painful extremities. About 1 month prior to admission the patient had returned from India, where she had a brief episode of diarrhea with fever that was treated with shots. Two days after returning from her trip, the patient was hospitalized with abdominal pain and diarrhea. Abdominal ultrasound revealed cholecystitis, and stool examination was positive for Blastocystis hominis, resulting in the patient's being started on metronidazole 750 mg three times a day. Two weeks later, she developed wrist and hand arthralgias and was prescribed ibuprofen and amitriptyline at night for sleep. Laboratory investigation at this time revealed an ESR of 24 mm/hr, normal complete blood counts, CK of 54, negative antinuclear antibodies screen, and mildly elevated rheumatoid arthritis factor at 66 IU/ml (reference, <40). One week later, she complained of difficulty in hearing and bilateral ankle pain. She denied any fever, chills, or night sweats. Examination did not reveal any inflammation of the …

DO NONIMMUNOLOGICALLY MEDIATED PATHWAYS PLAY A ROLE IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS?

The association between elevated serum rheumatoid factor and rheumatoid arthritis (RA) has been confirmed repeatedly and interpreted as strong evidence for an immunologic basis for the disease. In recent years, considerable additional evidence supporting this view has been obtained, strongly suggesting a role for CD4+ T cells in the pathogenesis of RA. An alternative view has also gained support, however. Based on studies of animal models and of RA itself, several lines of evidence have emerged that indicate that nonimmunologic pathways are operative in established RA. These observations have fostered the hypothesis that the evolution of RA may be associated with the emergence of non-T-cell-dependent autonomous pathways that dominate the latter stages of the disease.

リウマチ因子が異常高値を呈し，ｓｉｎｇｌｅ ｒａｄｉａｌ ｉｍｍｕｎｏｄｉｆｆｕｓｉｏｎ法によるＩｇＭの測定が，血しょう交換療法の指標に有効であったマクログロブリン血症の１例

リウマチ因子が異常高値を呈し，ｓｉｎｇｌｅ ｒａｄｉａｌ ｉｍｍｕｎｏｄｉｆｆｕｓｉｏｎ法によるＩｇＭの測定が，血しょう交換療法の指標に有効であったマクログロブリン血症の１例

Serum antibody responses to Streptococcus mutans antigens in humans systemically infected with oral streptococci.

Sera from patients with subacute bacterial endocarditis (SBE) due to Streptococcus mutans or other oral streptococci and from normal subjects were assayed by enzyme-linked immunosorbent assay for antibodies to defined S. mutans antigens. Antibodies of IgG and IgA isotypes to Ag I/II and Ag III were greatly elevated in S. mutans-SBE sera, and the IgA antibodies in 3 sera included both polymeric and monomeric forms. Elevated IgM and IgG anti-lipoteichoic acid and IgG and IgA anti-serotype c polysaccharide antibodies were also found. The sera of 4 of 6 patients infected with other oral streptococci also displayed antibodies to S. mutans Ag I/II. Sera of 3 patients infected with Streptococcus mitis or Streptococcus oralis, but none of the S. mutans-infected cases, showed elevated antibodies to human heart sarcolemma, and all SBE sera had elevated rheumatoid factor. These results suggest that the known surface protein antigens of S. mutans are immunodominant in humans, and are not likely to be heart cross-reactive.

Clinical Comparison of Immunoradiometric Assays for Intact Versus Beta-Specific Human Chorionic Gonadotropin

Monoclonal immunoradiometric assays (IRMA) for human chorionic gonadotropin (hCG) are available for either intact hCG (IhCG) or beta subunit hCG (beta hCG). The authors evaluated the clinical applications of both methods. Serum samples (N = 180) were divided into the following five clinical groups: Group 1: elevated luteinizing hormone (LH), follicular stimulating hormone (FSH), and thyroid-stimulating hormone (TSH), which share alpha subunits with hCG; Group 2: pregnancy; Group 3: trophoblastic tumors; Group 4: malignancy; and Group 5: positive rheumatoid factor or anti-nuclear antibody (ANA). The values of beta hCG versus IhCG for Group 1 showed statistical significance but no clinical significance, indicating negligible cross-reactivity in the alpha subunit group. beta hCG values, although exceeding the IhCG values, correlated well (r = 0.97) in intrauterine pregnancies; however, these values were not believed to be clinically significant. There is negligible interference by alpha subunits, elevated rheumatoid factor, ANA, or malignancy in the determination of IhCG versus beta hCG. The authors conclude that either the IhCG or beta hCG assays may be used in clinical conditions in which a potential exists for interference of alpha subunits, autoantibodies, or heterophile antibodies or in malignancy.

Rheumatoid factor induction in the mouse: sex differences and the effect of the sex steroids

Female CBA mice produced a significantly higher plasma rheumatoid factor (RF) response to Salmonella typhosa lipopolysaccharide than did male mice. The peak level in females was observed on day 5-6 after injection and in males on day 7-8. Elevated RF levels continued to be detected more than 30 days later. A second injection of LPS, 38 days after the first, to assess the secondary response, had no more than an additive effect on plasma RF concentration, although the day of peak response was earlier by two days in both sexes. Administration of oestradiol-17 beta by Silastic implant brought forward the day of peak response by two days in both sexes although it reduced its amplitude considerably. Testosterone had little effect on the peak concentrations achieved in both sexes, but did produce a slower decay in plasma RF level. This investigation indicates that the sex hormones can influence the response to LPS, a polyclonal B cell activator. This may have implications for the sex differences seen in autoimmune diseases.

Effects of Short-term Administration of Antipsychotic Drugs on Lymphocyte Subsets in Schizophrenic Patients

To the Editor.— Studies of various immunological parameters in schizophrenic patients are potentially confounded by the possible effects of neuroleptic medication on the immune system. Certain neuroleptic drugs, including the phenothiazines, chlorpromazine, and thioridizine, have been associated with the development of antinuclear-and and anti—single-stranded DNA antibodies, elevated serum rheumatoid factor, and even splenomegaly.1Clozapine, a dibenzodiazepine derivative, has been reported to produce a potentially lethal agranulocytosis in a small percentage of patients,2,3and therefore may have direct effects on hematopoiesis. In this issue of theArchives, we demonstrate that a subgroup of schizophrenic patients (approximately 30%) have elevated numbers of CD5+(Leu1) B lymphocytes.4This subset of B lymphocytes has been shown by several laboratories to be elevated in patients with certain autoimmune disorders.5-7The CD5+B lymphocytes are known to spontaneously proliferate in vitro8and preferentially produce autoantibodies.5,9,10In our study,4schizophrenic

Measurement of Rheumatoid Factor Isotypes in the Clinical Laboratory

In this study we assessed the clinical utility of measuring all major rheumatoid factor (RF) isotypes (IgG, IgA, and IgM) in the diagnostic immunology laboratory using an enzyme-linked immunoassay (ELISA). An improved method for IgG-RF was tested which employed a commercially available monoclonal anti-human IgG Fd antibody and did not require pepsin digestion of samples. We detected elevated levels of all three RF isotypes in a population of hospitalized rheumatoid arthritis patients (n = 109). We demonstrated a significant association between IgM and IgA RF which occurred in 36% of our subjects, while less than 6% had IgM + IgG RF or IgG + IgA RF. A comparison of the IgM ELISA with the Rheumaton revealed a statistically significant correlation (r = 0.65, p = 0.001). In addition, the two methodologies were equivalent in sensitivity (ELISA: 76%, Rheumaton: 78%). However, the ELISA procedure was more time consuming, costly, and required greater technical expertise. The following clinical and laboratory findings were significantly associated with RF isotypes: IgG RF and the presence of rheumatoid nodules (p = 0.03), elevated erythrocyte sedimentation rate (ESR) and IgG RF (p = 0.007), and elevated ESR and IgM RF (p = 0.0009). Our ELISA methodology did not provide significant advantages over existing techniques to justify its use as part of the routine laboratory assessment of rheumatoid factor.

Rheumatoid factor isotypes and renal disease in systemic lupus erythematosus.

There is no agreement on whether rheumatoid factor (RF) exerts protection, injury, or is an epiphenomenon with regard to kidney disease in systemic lupus erythematosus (SLE). In this study we examined the occurrence and isotype distribution of rheumatoid factor in SLE in relation to some clinical parameters, including renal function and arthritis. A highly significant correlation (p less than 0.001) was noted between the presence of IgG RF and absence of kidney disease. The IgG RF also seemed to protect SLE patients from developing arthritis (p less than 0.01). On the other hand, elevated IgM RF levels indicated active SLE disease. The results obtained are discussed in relation to the ability of RF to interact with immune complexes in vitro and in vivo.

Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies.

Circulating immune complexes (CIC) containing IgA and C3 were elevated in 48% of IgA nephropathy patients; IgA1 was the predominant subclass. IgA1-IgG CIC were detected in 44%, IgA2-IgG CIC in 7%, and IgM-IgA1 CIC in 16% of the patients. No IgM-IgA2 CIC were detectable. Sucrose gradient ultracentrifugation indicated that IgG-IgA1 CIC were predominantly of intermediate (13-19S) size whereas IgA1-C3 CIC sedimented from 11S to 19S. At acid pH, isolated CIC revealed the presence of substantial amounts of 7S IgA. One third of the patients had elevated serum IgA rheumatoid factor (RF) of both polymeric and monomeric forms despite normal levels of IgM-RF; 87% of patients with elevated IgA-RF had IgA1-IgG CIC. These results indicate that the IgA1 component of CIC in patients with IgA nephropathy is not necessarily of mucosal origin and suggest that a portion of these CIC consists of IgA RF immunologically complexed with autologous IgG.

Synthesis of measles virus‐specific IgM antibodies and IgM‐class rheumatoid factor in relation to clinical onset of subacute sclerosing panencephalitis

Thirty-seven serum and 37 cerebrospinal fluid (CSF) specimens from 27 patients with subacute sclerosing panencephalitis (SSPE) were tested for measles virus (MV) IgM antibodies and IgM-class rheumatoid factor (RF) to determine if a temporal relationship exists between SSPE onset and these immunoglobulins. Sensitive solid-phase radioimmunoassays were used for immunoglobulin detection. Five of six MV IgM-positive CSF, both MV IgM-positive sera and six out of eight sera with elevated RF levels were collected within 1 yr of SSPE onset. Also collected during this time were six other sera having high binding in the MV IgM assay, which was not due to MV-specific IgM antibodies. Two of these sera had as high or higher binding of IgM to a Vero cell control antigen, suggesting involvement of an IgM-class autoantibody. The other four sera had false-positive MV IgM assay results due to RF interference. RF interference was dependent on both the titer and avidity of the MV IgG antibodies involved. Three conclusions can be drawn from these results. First, MV IgM antibodies and elevated RF levels are not markers for acute SSPE, despite the tendency for their synthesis at this stage of the disease. Second, immunoassay analysis of viral IgM antibodies must employ an appropriate control antigen to account for background IgM binding. Finally, even if RF levels are normal or near normal, a false-positive IgM immunoassay result can still occur if antigen-specific IgG antibodies in the same sample have the right combination of titer and avidity.

A rapid solid phase assay for the detection of circulating immune complexes

A simplified process, which we have termed Enzyme Immune Complex Assay (EICATM) for the detection of circulating immune complexes (CICs), is described herein. The method utilizes readily available reagents, small quantities of serum, and can be performed quickly with a minimal amount of equipment. Serum from 38 normal controls, 98 burn patients, 36 frostbite injury patients, and 21 patients with elevated rheumatoid factor (RF) were tested for CICs in an immune function study. Elevated immune complex levels were found in the group of patients with frostbite injury, and in the group with elevated RF. Serum from thermally injured patients had slightly depressed yet normal CIC levels. The detection of elevated CICs by the EICATM method compared favorably with the more cumbersome Raji cell method, with the added advantage of simplicity, speed, and the ability to detect non-IgG immune complexes.

Pulmonary Immune Complex Deposition in Wegener's Granulomatosis

Two male patients with pulmonary manifestations of Wegener's granulomatosis are presented. One had an elevated rheumatoid factor, and both had elevated levels of immunoglobulin E. Both demonstrated characteristic necrotizing granulomatous lesions on light microscopy of lung tissue. Immunohistologic analysis of lung tissue demonstrated a granular deposition of immunoglobulin G and complement. Raji cell assay of sera demonstrated elevated levels of circulating immune complexes in the sera of the one patient tested prior to any therapy. These findings support the hypothesis that immune complex deposition contributes to the pathogenesis of Wegener's granulomatosis.

IgM-class rheumatoid factor in serum and cerebrospinal fluid of multiple sclerosis and matched neurological control patients

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 matched neurological control (NC) patients were quantitatively tested for IgM-class rheumatoid factor (RF). Significantly elevated RF levels were found in serum from 6 MS patients and 12 NC patients. Seven of the latter 12 patients had a diagnosis of recurrent head pain. RF was detected in CSF from 2 MS patients and 2 NC patients. In 3 of the 4 cases, this could be explained by blood-brain barrier damage or normal diffusion of RF into CSF. Intrathecal RF synthesis was found in the remaining MS patient. These results suggest that RF production may be related to underlying pathological mechanisms in at least some MS and NC patients. They also confirm that RF must be carefully accounted for in etiological studies designed to demonstrate pathogen-specific IgM antibodies in, for example, MS patients.

Rheumatoid Nodulosis A Relatively Benign Rheumatoid Variant

Subcutaneous nodules and rheumatoid factor (RF) are criteria used to diagnose rheumatoid disease. Their presence correlates with disease severity and poorer prognosis. They have been reported, however, in patients with little arthritis and no systemic disease. We studied four such patients, in whom (1) RF was present in high titer; (2) nodules were often extensive (nodulosis) and involved elbows, hands, and feet, with a predilection for tendons; and (3) roentgenograms showed large, subchondral bone cysts without cortical erosion of correlation with nodule location. The conditions of three of these patients had been previously misdiagnosed as gout or xanthoma. Our findings were similar to those in seven other patients described in earlier reports. We suggest that nodulosis, bone cysts, and elevated RF with little active arthritis constitute a relatively benign variant of rheumatoid disease.

A rapid method for immune complex detection: PEG insolubilization combined with laser nephelometry

Abstract A rapid simple method is described for the detection of immune complexes. The PEG-induced insolubilization of aggregated IgG and bovine serum albumin : anti-bovine serum albumin (BSA : anti-BSA) complexes produces a turbidity which increases with PEG concentration, is quantitated by means of light scatter and measured by laser nephelometry. Monomeric and heat-aggregated IgG from 0.5 μg to 32 μg per reaction tube were tested for light scatter in borate buffer and in 1–5% PEG. Monomeric IgG produced no light scatter in borate and less than 0.4% light scatter in all concentrations of PEG. Aggregated IgG in borate generated no light scatter. However, 1 μg aggregated IgG or more gave enhanced light scatter in PEG. This light scatter increased with the amount of aggregated IgG and with PEG concentration. BSA : anti-BSA complexes were prepared at antigen : antibody ratios from 4 to 16 times antigen excess. The resulting soluble complexes of different sizes were tested in borate buffer and 2%, 2.5% and 3% PEG. Complexes in buffer produced little light scatter, but PEG greatly enhanced their light scatter. The degree of enhancement by PEG increased linearly with complex concentration. Both antigen and antibody were demonstrated in the PEG-insolubilized complexes. Preliminary experiments with human serum have demonstrated 1.3% RLS in 60% of sera with elevated rheumatoid factor titers.

IgA rheumatoid factor in the sera and saliva of patients with rheumatoid arthritis and Sjögren's syndrome.

With a sensitive radioimmunoassay we have found elevated IgA rheumatoid factor (IgA-RF) levels in the sera of patients with rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. The IgA--RF showed a pattern of reaction with human IgG subclasses and animal gammaglobulins similar to that of IgM-RF from the same patients. Rheumatoid factors of both classes were shown to be present in saliva of patients with rheumatoid arthritis and Sjögren's syndrome.