Human parvovirus B19 infection in patients with systemic lupus erythematosus

OBJECTIVE: The clinical significance of the presence of B19 DNA in patients with SLE was studied. METHODS: Sera from 72 patients with systemic lupus erythematosus (SLE), 23 patients with rheumatoid arthritis (RA), 18 patients with Sj?gren's syndrome (SS), eight patients with Raynaud's phenomenon (RP), five patients with primary biliary cirrhosis (PBC), five patients with polymyositis (PM), four patients with erythema infectiosum (EI) and 22 normal controls were examined for parvovirus B19 (B19) infection by serological assays, nested PCR and Southern blotting. RESULTS: Parvovirus B19 DNA was detected in 17 of 72 patients with SLE and in three of four patients with EI, but not in patients with other systemic rheumatic diseases. Of the 17 patients with B19 DNA, only one had IgG anti-B19 antibody and two had IgM anti-B19 antibodies, whereas IgG and IgM anti-B19 antibodies were detected in 27 (49.1%) and 21 (38.2%) of 55 SLE patients without B19 DNA respectively. All sera from the patients with EI contained both IgG and IgM anti-B19 antibodies. B19 DNA was found more commonly in sera from SLE patients without anti-B19 antibodies than in those with anti-B19 antibodies (P<0.05). CONCLUSIONS: B19 infection in patients with SLE may be due to lack of anti-B19 antibodies because of either the immunocompromised nature of the host or the use of immunosuppressive drugs. There was a higher prevalence of hypocomplementaemia and RP in patients with parvovirus B19 viraemia than in those without parvovirus B19 viraemia.     

Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients

In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported.     

Anti-DNA and antilymphocyte antibodies during acute infection with human parvovirus B19

Sera from patients in the acute and recovery stages of parvovirus B19 infection, and from individuals with no detectable antiparvovirus antibody were examined for the presence of anti-DNA and antilymphocyte antibodies. Sixty-eight percent of individuals recently recovered from parvovirus infection had elevated levels of antidouble stranded (ds) and antisingle stranded (ss) DNA antibodies. In addition, a cytotoxic IgM antilymphocyte antibody was detected in more than 88% of these same sera. Serial specimens from volunteers experimentally infected with parvovirus B19 were also tested for these autoantibodies and it was determined that the presence of antilymphocyte IgM was dependent on the stage of infection. The antilymphocyte IgM was occasionally detectable in sera containing rubella specific IgM (11%) or varicella zoster specific IgM (25%). However, in contrast to B19 infection, these antibodies were not cytotoxic. From the results of our study, we propose that parvovirus infection of hematologically normal individuals may be accompanied by a transient, subclinical autoimmune state.     

Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the development aplastic crises

The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE), Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140) have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05) was seen between IgG antibody prevalence in male (27.8%) and female (35.5%) patients. Anti-B19 IgG antibodies were more frequent in older (37.6%) than younger (28.2%) than 20 years old patients, although this difference had no statistical significance (p > 0.05). Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.     

Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus

Objective. To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection. Methods. Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of β₂-glycoprotein I (β₂-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity. Results. Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of β₂-GPI as a binding cofactor, similar to aCL found in SLE patients, but unlike antibodies from patients with other viral infections or from those with syphilis. Conclusion. The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.     

Association between human parvovirus B19 infection and arthritis.

OBJECTIVE--To gain information concerning the association between parvovirus B19 infection and arthritis. METHODS--Blood or synovial fluid, or both, from a total of 77 adult patients with various arthropathies (rheumatoid arthritis 13; mechanical arthropathies 11; crystal induced arthritis 13; idiopathic mono/oligoarthritis 25; suspicion of viral arthritis 15) were tested for the presence of the viral genome and anti-B19 antibodies. B19 DNA in blood and synovial fluid was investigated by nested polymerase chain reaction, and anti-B19 IgM and IgG antibodies were detected in blood by enzyme immunoassay. RESULTS--A recent parvovirus infection was documented by the presence of anti-B19 IgM antibodies in the blood of 13 patients. B19 DNA, together with anti-B19 IgM and IgG antibodies, were detected in the blood of seven patients who had an acute transient arthritis, putatively of viral origin. Viral DNA was detected in a synovial fluid sample and in the blood of one patient with monoarthritis who had an anti-B19 IgG response only. CONCLUSIONS--The prevalence of anti-B19 IgG antibody in these patients with various forms of arthritis (63%) was within the same range as that in the general population (blood donors). However, for the patients with clinical suspicion of viral arthritis, the increased seroprevalence of anti-B19 IgM and the presence of the B19 genome point to an association between human parvovirus infections and acute forms of arthritis.     

Value of IgA anticardiolipin and anti-beta2-glycoprotein I antibody testing in patients with pregnancy morbidity

OBJECTIVE: To study the prevalence of IgA antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein I (abeta(2)GPI), in a cohort of patients with pregnancy morbidity. PATIENTS AND METHODS: Serum samples from four groups of patients were studied by an in house enzyme linked immunosorbent assay (ELISA). Group I: 28 patients with primary antiphospholipid syndrome (PAPS) (median age 32.5 years, range 25-34). Twelve patients had a history of thrombosis. All were positive for IgG/M aCL or lupus anticoagulant (LA), or both. Group II: 28 patients with unexplained pregnancy morbidity (median age 35 years, range 23-48). Seven had history of thrombosis. Nine patients were positive for IgG/M aCL. None from this group fulfilled Sapporo criteria for APS. Group III: 28 patients with systemic lupus erythematosus (SLE) (median age 34 years, range 25-52). Eleven had a history of thrombosis. Twenty one patients had IgG/M aCL and/or LA, but only 19 fulfilled Sapporo criteria for APS. RESULTS: IgA aCL were found in 12, 6, and 14 patients from the groups with PAPS, unexplained pregnancy morbidity, and SLE, respectively. Most patients had these antibodies together with IgG/IgM aCL. Three patients from the group with unexplained pregnancy morbidity and two with SLE had IgA aCL alone. IgA abeta(2)GPI was present in one patient from each group. All IgA abeta(2)GPI were present together with IgG and/or IgM abeta(2)GPI. CONCLUSIONS: The prevalence of IgA aCL is high in patients with pregnancy morbidity, although IgA aCL are usually present together with IgG and/or IgM aCL. IgA abeta(2)GPI are not useful in identifying additional women with APS and pregnancy morbidity.     

High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa

OBJECTIVE: To investigate possible correlations between cutaneous polyarteritis nodosa (CPN) and antiphospholipid syndrome-associated antibodies. METHODS: Sixteen patients were referred with CPN features. To investigate the possible role of antiphospholipid antibodies (aPL) in CPN, we measured serum lupus anticoagulant (LAC), IgG and IgM anticardiolipin (aCL) and anti-phosphatidylserine-prothrombin complex (anti-PS/PT) antibodies, and anti-beta(2)-glycoprotein I-dependent cardiolipin (anti-beta(2)GPI/CL) antibodies in the 16 CPN patients, 8 microscopic polyangiitis (MPA) patients, 33 systemic lupus erythematosus (SLE) patients, and 23 healthy controls. LAC was determined according to the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibody guidelines. Anti-PS/PT, aCL, and anti-beta(2)GPI/CL antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Anti-PS/PT antibodies and/or LAC were detected in all CPN patients, but not in any controls. Serum IgM anti-PS/PT antibody was found in 13 (81.3%) CPN patients. The mean +/- SD serum anti-PS/PT IgM level (19.9 +/- 12.4 units/ml) in CPN patients was significantly elevated compared with SLE patients (5.7 +/- 5.9 units/ml). IgG anti-PS/PT antibody was detected in 5 (31.3%) CPN patients, but not in any controls. The IgG PS/PT antibody titers were similar in CPN patients (12.3 +/- 12.0 units/ml) and SLE patients (13.8 +/- 14.3 units/ml). Three (18.8%) CPN patients were positive for IgG aCL antibody and 2 (12.5%) for IgM aCL antibody. No MPA patients had aPL. CPN skin manifestations included livedo reticularis (14 [87.5%]). Direct immunofluorescence (DIF) revealed C3 within the affected vessels in 7 (77.8%) of 9 CPN patients. CONCLUSION: Our study demonstrated that presence of anti-PS/PT antibodies and/or LAC could serve as markers in CPN patients. CPN could be dependently associated with the presence of anti-PS/PT antibody. Clinicians need to recognize these titers to permit early accurate diagnosis and treatment. We believe that anti-PS/PT antibodies will become widely recognized as a new factor when diagnosing CPN.     

Parvovirus B19 may have a role in the pathogenesis of juvenile idiopathic arthritis

OBJECTIVE: To determine the prevalence of human parvovirus B19 infection in patients with juvenile idiopathic arthritis (JIA) by detection of specific IgM, IgG, and viral DNA. METHODS: Serum samples of 50 patients with diagnosis of JIA and 39 healthy controls were analyzed by ELISA to detect IgG and IgM anti-B19-specific antibodies. The parvovirus B19 genome was detected by nested polymerase chain reaction (PCR). The average age of the patients was 9.6 years (2-14 yrs); 30 were female (60%) and 20 male (40%). The definitive diagnoses of these patients corresponded to 19 systemic forms (38%), 11 to the oligoarticular variety (22%) and 20 to the polyarticular (40%). The average age of the control group was 7.8 years (2-16 yrs); the distribution by sex was 25 females (64%) and 14 males (36%). RESULTS: IgM against parvovirus B19 was detected in 20% of the cases (10 patients) and B19 DNA genome by PCR in 48% (24 patients); in 10% of the cases (5 patients), both markers were detected. IgG was found in 32% (16 patients). In the control group neither IgM nor the viral genome was detected. However, 43.5% of the controls (17/39) had IgG against parvovirus B19, indicating past infection by the virus. CONCLUSION: Our study confirms recent observations regarding a high prevalence of viral DNA in JIA patients and a possible role of this viral infection in JIA pathogenesis.     

Late thrombotic events in patients with temporal arteritis and anticardiolipin antibodies

IgG and IgM isotypes of anticardiolipin (aCL) antibodies were measured in a group of 40 patients with biopsy-proven temporal arteritis (TA), 13 of them with ischemic complications related to the disease. High levels of aCL antibodies were found in only 3 (7.5%) patients. Two had high titres of both IgG and IgM isotypes and the third had high titres of the IgM isotype. No relationship between aCL antibody positivity and the development of any of the classical early occlusive complications of TA was found. However, 2 out of the 3 patients with positive aCL antibody titres later developed ischemic phenomena on conventional corticosteroid treatment. This finding suggests that aCL antibodies could perhaps have a role in the development of the late ischemic complications that occasionally occur in adequately treated TA patients.     

Antiphospholipid antibody in localised scleroderma

OBJECTIVE: To investigate the prevalence and clinical correlation of antiphospholipid antibodies in localised scleroderma. METHODS: Antibodies against cardiolipin (aCL) or beta(2)-glycoprotein I were examined by enzyme linked immunosorbent assay (ELISA) in 48 patients with localised scleroderma (18 patients with generalised morphoea, 20 with linear scleroderma, and 10 with morphoea). Twenty one of these patients were investigated for lupus anticoagulant (LAC) by screening and confirmatory coagulation tests. RESULTS: Patients with generalised morphoea, the severest form of localised scleroderma, had significantly raised levels of IgM or IgG aCL relative to normal controls (n=21) and patients with systemic sclerosis (n=20). The IgM isotype was predominant, with the frequency of IgM aCL (61%) higher than that of IgG aCL (28%). Levels of aCL were similar for patients with linear scleroderma or morphoea and normal controls. IgM aCL were associated with a greater number of lesions, especially plaque lesions, wider distribution of lesions, and the presence of immunological abnormalities including antinuclear antibodies, rheumatoid factor, IgM antihistone antibodies, IgG anti-single stranded DNA antibodies, and raised serum interleukin 6 levels in patients with localised scleroderma. LAC was detected in 5/7 (71%) patients with generalised morphoea. However, pulmonary embolism was seen in only one patient with generalised morphoea. None of patients with localised scleroderma exhibited anti-beta(2)-glycoprotein I antibodies. CONCLUSIONS: These results suggest that aCL and LAC are the major autoantibodies in patients with generalised morphoea.     

Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19 infection as a pitfall

BACKGROUND: While antibodies directed against proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA) have a high specificity for the diagnosis of systemic vasculitis, they may also be found as an epiphenomenon of acute viral infection. OBJECTIVE: To investigate whether positive ANCA test results may be a common feature of acute parvovirus B19 infection. METHODS: Sera were analysed from 1242 patients from a rheumatology outpatient clinic for reactivity with parvovirus B19 and EBV antibodies. They were tested for the presence of PR3-ANCA and MPO-ANCA, along with sera known to contain IgM antibodies to these viruses obtained from among 41,366 samples submitted for virological screening. RESULTS: ANCA were found in 10% (5/50) of the sera positive for IgM antibodies to parvovirus and in 3/51 sera containing IgM antibodies to EBV. Three of six patients with arthritis and concomitant parvovirus infection were found positive for PR3-ANCA and two were found positive for MPO-ANCA. All six patients tested negative for ANCA after six months of follow up. CONCLUSIONS: PR3-ANCA and MPO-ANCA may occur transiently in patients with acute B19 infection or infectious mononucleosis, highlighting the importance of repeated antibody tests in oligosymptomatic clinical conditions in which systemic autoimmune disease is suspected.     

Rheumatologic manifestations of human parvovirus B19 infection in adults. Initial two-year clinical experience

During 1987 and 1988, we identified 9 adults at the Medical and Rheumatology Services of the University of Iowa Hospitals and Clinics who had a clinical diagnosis of fifth disease; 8 of the 9 had symptoms of joint involvement. Another 12 adults with serologic positivity for anti-parvovirus B19 IgM antibody presented with polyarthralgia/polyarthritis. Patients were usually found to be seronegative for rheumatoid factor, and none developed nodules or erosive disease. Many patients with chronic disease met criteria for a diagnosis of rheumatoid arthritis. A diagnosis of parvovirus B19 infection should be considered during the initial visit of patients with polyarthralgia/polyarthritis.     

Anticardiolipin antibody positivity in diabetic patients with and without diabetic foot

Anticardiolipin (aCL) antibodies may play a role in the enhancement of platelet aggregation and/or progression of the macrovascular diabetic complications. Also, aCL antibodies may cause or promote ischemia and thrombosis. Therefore, we aimed to investigate IgG aCL and IgM aCL antibodies positivity in type 2 diabetic patients with and without ischemic diabetic foot. In this case-control study, we examined 40 diabetic patients without diabetic foot problem and 35 diabetic patients with ischemic diabetic foot. Forty diabetic patients (19 females, 21 males) without diabetic foot served as Group 1 and 35 diabetic patients (17 females, 18 males) who had ischemic diabetic foot served as Group 2. In the control group, 35 nondiabetic healthy subjects (18 females, 17 males) were included in Group 3. The groups were similar in age and sex, which is not statistically significant (P>.05). There was no difference in the IgG aCL antibodies positivity between Groups 1 and 3 (P>.05). However, IgG aCL antibodies positivity in Group 2 was significantly higher than those of the other groups (P<.05). IgG aCL antibodies were found positive in 10% (4/40) of Group 1, 34.3% (12/35) of Group 2 and 8.6% (3/35) of Group 3. When Groups 1 and 2 were compared, the odds ratio adjusted for age, gender, hypertension, coronary artery disease history, cigarette smoking, duration of diabetes mellitus, cholesterol, and haemoglobin A(1C) (HbA1c) was 6.8 [95% confidence interval (CI), 1.41-32.66; P=.016] for aCL positivity. In conclusion, although available evidence does not prove a causal association between positivity of aCL and diabetic foot, we believe that a causal association is supported by the data obtained from this study.     

Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective analysis of a series of 100 patients.

A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) in a series of 100 patients with systemic lupus erythematosus was carried out. To determine the normal range of both isotype titres a group of 100 normal control serum samples was studied and a log-normal distribution of IgG and IgM isotypes was found. The IgG anticardiolipin antibody serum was regarded as positive if a binding index greater than 2.85 (SD 3.77) was detected and a binding index greater than 4.07 (3.90) was defined as positive for IgM anticardiolipin antibody. Twenty four patients were positive for IgG aCL, 20 for IgM aCL, and 36 for IgG or IgM aCL, or both. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM aCL with haemolytic anaemia and neutropenia. Specificity and predictive value for these clinical manifestations increased at moderate and high anticardiolipin antibody titres. In addition, a significant association was found between aCL and the presence of lupus anticoagulant. Identification of these differences in the anticardiolipin antibody isotype associations may improve the clinical usefulness of these tests, and this study confirms the good specificity and predictive value of the anticardiolipin antibody titre for these clinical manifestations.     

High titer of anti–phosphatidylserine‐prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa

Objective

To investigate possible correlations between cutaneous polyarteritis nodosa (CPN) and antiphospholipid syndrome–associated antibodies.

Methods

Sixteen patients were referred with CPN features. To investigate the possible role of antiphospholipid antibodies (aPL) in CPN, we measured serum lupus anticoagulant (LAC), IgG and IgM anticardiolipin (aCL) and anti–phosphatidylserine‐prothrombin complex (anti‐PS/PT) antibodies, and anti–β₂‐glycoprotein I–dependent cardiolipin (anti‐β₂GPI/CL) antibodies in the 16 CPN patients, 8 microscopic polyangiitis (MPA) patients, 33 systemic lupus erythematosus (SLE) patients, and 23 healthy controls. LAC was determined according to the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibody guidelines. Anti‐PS/PT, aCL, and anti‐β₂GPI/CL antibodies were measured by enzyme‐linked immunosorbent assay.

Results

Anti‐PS/PT antibodies and/or LAC were detected in all CPN patients, but not in any controls. Serum IgM anti‐PS/PT antibody was found in 13 (81.3%) CPN patients. The mean ± SD serum anti‐PS/PT IgM level (19.9 ± 12.4 units/ml) in CPN patients was significantly elevated compared with SLE patients (5.7 ± 5.9 units/ml). IgG anti‐PS/PT antibody was detected in 5 (31.3%) CPN patients, but not in any controls. The IgG PS/PT antibody titers were similar in CPN patients (12.3 ± 12.0 units/ml) and SLE patients (13.8 ± 14.3 units/ml). Three (18.8%) CPN patients were positive for IgG aCL antibody and 2 (12.5%) for IgM aCL antibody. No MPA patients had aPL. CPN skin manifestations included livedo reticularis (14 [87.5%]). Direct immunofluorescence (DIF) revealed C3 within the affected vessels in 7 (77.8%) of 9 CPN patients.

Conclusion

Our study demonstrated that presence of anti‐PS/PT antibodies and/or LAC could serve as markers in CPN patients. CPN could be dependently associated with the presence of anti‐PS/PT antibody. Clinicians need to recognize these titers to permit early accurate diagnosis and treatment. We believe that anti‐PS/PT antibodies will become widely recognized as a new factor when diagnosing CPN.     

Clinical manifestations and antiphosphatidylserine antibodies in patients with systemic lupus erythematosus: is there an association?

Objective: Antiphospholipid antibodies are a group of heterogeneous autoantibodies which have been reported in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and thrombocytopenia. In this study, we aimed to reveal the prevalence and correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE patients. Methods: Fifty-nine SLE patients and 41 healthy controls were included. Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were performed by enzyme-linked immunosorbent assay. Results: All isotypes of aCL and aPS antibodies except IgG were higher in patients with or without APS than those in the healthy controls (p<0.001). The most significant associations were found among migraine and IgA aCL (p<0.001), livedo reticularis and both IgM aCL and IgM aPS (p<0.001), migraine and IgM aCL (p<0.01), pulmonary involvement and IgM aCL (p<0.01), migraine and IgA aPS (p<0.01), and both thrombosis and migraine with IgM aPS (p<0.01). Conclusion: A relatively high prevalence of aCL and aPS antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM aPS with thrombosis in SLE patients with secondary APS. The assessment of both IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these manifestations.     

Anticardiolipin antibody determination: comparison of three ELISA assays

The aim of this study was to compare two commercial kits (A and B) with our our own assay (C) for the determination of anticardiolipin antibodies (aCL). In 42 controls no subject was found to be aCL positive with kit A, seven were aCL positive with kit B and 1 with assay C. In 61 patients, the results were as follows: 50.8% aCL positivity for A, 57.4% for B and 50.8% for C. Only 57.3% of the patients were either positive (20 patients) or negative (15 patients) in the three tests. As for controls the concordance in patients was better between kit A and assay C than between kit B and assay C. Another group of patients with high IgM blank values in assay C were selected; when their blank values as measured with the kits were subtracted, 40% of the aCL positive patients with kit A became negative. In summary this comparison indicates that aCL positivity may vary according to the assay used and that non-specific binding may lead to false positive results.     

Cytopenia and past human parvovirus B19 infection in patients with primary Sjögren's syndrome

OBJECTIVES: To determine the clinical significance of human parvovirus B19 infection in patients with primary Sj?gren's syndrome (SS) and to investigate the immunologic and hematologic features related to B19 infection. METHODS: We included 80 consecutive patients with primary SS (74 women and 6 men), with a mean age of 62 years (range, 24 to 87 years) that were seen in our Unit. All patients fulfilled the European Community criteria for SS. As controls, we included 140 consecutive sera samples analyzed for B19 antibodies in our Microbiology Department and obtained from adult inpatients and outpatients of our Hospital. Serum from all patients and controls was tested for antibodies to B19 by enzyme-linked immunosorbent assay (ELISA). Additionally, the presence of B19 DNA in serum and in circulating leukocytes was investigated by nested polymerase chain reaction (PCR). RESULTS: Serological evidence of past B19 infection (positive IgG antibodies without IgM antibodies) was present in 28 (35%) patients with primary SS. None of these patients showed evidence for B19 viremia, and B19 virus DNA was not detected in the circulating leukocytes of IgG-B19(+) patients. Positivity for IgM antibodies to B19 was not detected in any patient. When compared with patients without evidence of past B19 infection, those with primary SS and past B19 infection showed a higher prevalence of cytopenia (57% v 15%; P < .001), and, specifically, of leukopenia (36% v 4%; P < .001). Additionally, when compared with controls positive for IgG-B19, SS patients with these antibodies had a higher prevalence of cytopenia (57% v 13%; P < .001), leukopenia (36% v 3%; P < .001) and thrombocytopenia (21% v 0%; P = .003). CONCLUSIONS: Serological evidence of past B19 infection is associated with the presence of cytopenia in our patients with primary SS. A possible relationship between B19 infection and the presence of cytopenia in primary SS may occur in some patients immunologically or genetically predisposed.     

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis

OBJECTIVE: Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. METHODS: Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P. mirabilis, Escherichia coli and other potentially arthritogenic organisms (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation end-products (anti-IgG-AGE) were measured. RESULTS: IgM and IgA anti-Proteus antibodies were significantly higher in patients with RF-positive RA compared with all other patient groups (P < 0.0005 and P < 0.005). Anti-P. mirabilis IgG, and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did not differ in the patient groups. IgM antibodies to E. coli were elevated in RF-positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by false-positive reactions, because after absorption of RF there was no decrease in antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were highest in patients positive for both RF and anti-IgG-AGE antibodies (P<0.001). Patients with erosions tended to have higher IgA anti-Proteus titres, but no association with the shared HLA epitope or treatment was detected. CONCLUSION: Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are associated with early seropositive RA and the presence of anti-IgG-AGE antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA requires further investigation.