High frequency of reactive arthritis in adults after Yersinia pseudotuberculosis O:1 outbreak caused by contaminated grated carrots.

OBJECTIVE: We describe the epidemiological and microbiological process in the clearing of a foodborne outbreak of Yersinia pseudotuberculosis O:1 linked to raw carrots and frequency of the associated reactive extra-gastrointestinal manifestations. METHODS: The patient samples were investigated by routine culture or antibody testing methods. The real-time bacterial PCR was used to detect Y pseudotuberculosis in samples from the grated carrots and in those taken from the carrot storage. Genotype of bacterial isolates was determined by pulsed-field gel electrophoresis. For case identification, we retrospectively looked over the laboratory files of the central hospital focusing on the time period of the outbreak. RESULTS: Altogether 49 case patients were identified. Y pseudotuberculosis was detected by real-time PCR analysis in samples taken from grated carrots and from the carrot distributor. Bacterial isolates originating from the farm environment showed identical serotype (O:1) and genotype (S12) with the patients' isolates. Among 37 adults, reactive arthritis (ReA) was found in 8 (22%) and three adults had probable ReA. Six (67%) out of nine human leucocyte antigen (HLA) typed patients with ReA were HLA-B27 positive. Erythema nodosum was found in 42% of the 12 children, whereas none of them had definite ReA. CONCLUSIONS: In this outbreak, Y pseudotuberculosis was for the first time detected in both patient and food samples. ReA was more common than earlier reported in the outbreaks associated with this pathogen; the reason may be that the previous outbreaks have occurred among children. HLA-B27 frequency was higher than usually reported in single-source outbreaks of ReA.

The outcome of pregnancy in antinuclear antibody-positive women.

The significance of antinuclear antibodies (ANA) was studied in 51 ANA-positive women who had had a total of 170 pregnancies. 60 ANA-negative age- and parity-matched women with a total of 142 pregnancies served as controls. The perinatal mortality rate in the ANA-positive group was 18.6% (8/43), while there were no perinatal deaths in the ANA-negative control group. All the perinatal losses were stillbirths. The rate of spontaneous abortions was low in both groups, 2.0 vs. 3.3%, respectively. The ANA titer, complement-fixing activity and antigenic specificity did not correlate with the outcome of the pregnancy. Two infants of the ANA-positive women (3.9%) had a congenital atrioventricular heart block. In both cases the ANA was of the complement-fixing type.

Defective erythrocyte C3b receptor function associated with low serum complement (C3, C4) concentrations in insulin-dependent diabetes mellitus.

An immune adherence haemagglutination (IAHA) method was used to measure erythrocyte C3b receptor (EC3bR) activity in 110 patients with insulin-dependent diabetes mellitus (IDDM) and 223 controls. Results obtained from IDDM were correlated with serum complement concentrations (C3, C4) as well as with HLA types of the patients. We observed an increased frequency of defective EC3bR in IDDM (26.4%) compared to controls (10.8%, P less than 0.0005). Those patients who had defective EC3bR (IAHA negative) also had lower serum C3 and C4 concentrations than those with normal EC3bR function (IAHA positive). HLA-Dw3 positive patients had lower C4 concentrations than HLA-Dw3 negative patients and more often had defective EC3bR activity, although this difference was statistically not significant. Our results may indicate the close relationship between the risk factors which predispose to both IDDM and systemic lupus erythematosus.

Chronic myelocytic leukaemia: HLA association and decreased erythrocyte C3b receptor expression.

A series of 27 adult patients with chronic myelocytic leukaemia (CML) were examined for erythrocyte C3b receptor (EC3bR) expression. Twenty-five patients were successfully HLA typed and there was a positive association of CML with HLA-B40 (P less than 0.01). Only 10 (37%) of the patients were EC3bR positive (P less than 0.00001) compared to 223 healthy controls of whom 198 (89%) were EC3bR positive. The positivity of EC3bR and HLA-B40 occurred simultaneously in six patients (P less than 0.05). HLA-B40 positivity and EC3bR expression were correlated with the following variables: age at the time of CML diagnoses, duration of CML (until death or the end of follow-up period 1 July 1983), the stage of CML and simultaneous medication. EC3bR positive patients were significantly more often in remission (P less than 0.05) and also had shorter duration of the disease (P less than 0.005) then did EC3bR negative ones. No significant correlation existed between EC3bR status and the other parameters. The presence of HLA-B40 did not associate with any of the listed variables. These findings may indicate the loss of the receptor in the course of CML with increasing immaturity of cells released from bone marrow.

Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon?

Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon.

Rheumatoid arthritis with pleural effusion includes a subgroup with autoimmune features and HLA-B8, Dw3 association.

Twenty-eight patients with rheumatoid pleural effusion were investigated to examine the frequency of HLA antigens as compared with 56 rheumatoid arthritis (RA) patients without this intrathoracic manifestation of RA and with 283 healthy controls. HLA-B8 was strongly associated with the presence of pleural effusion (PE) in RA patients. A high prevalence (71%) of B8/Dw3 was found among male RA patients of the PE group in whom the joint disease had begun at an age over 50 years and who also had besides pleuritis other intrathoracic manifestations of RA associated with high rheumatoid factor titres and low complement (C4) levels in sera. Actually, the HLA-B8 association was not seen in the rest of the PE group. The finding may be related to the heterogeneity of RA, a male subgroup of the disease being characterized by multiple intrathoracic manifestations and genetically associated with the large group of autoimmune disorders, such as SLE, characterized by high prevalences of HLA-B8 and D(R)3.

Diffuse interstitial lung disease in rheumatoid arthritis. Views on immunological and HLA findings.

Immunological parameters including HLA typing were studied in 32 patients with rheumatoid arthritis (RA) associated diffuse interstitial lung disease (DILD) and in 32 age- and sex-matched RA control patients. The male RA patient group with DILD also included patients with other intrathoracic manifestations and had a higher prevalence of HLA-B8 and Dw3 than did healthy controls, thus agreeing with our earlier results that RA patients with this antigen combination are prone to multiple intrathoracic complications. Patients with DILD had higher titres of rheumatoid factor (RF) and lower complement (C4) levels than matched RA controls. The RF titre was in inverse correlation with C3 and C4 levels, suggesting that RF immune complexes may also promote rheumatoid lung disease via activation of the classical pathway of complement.

Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases.

More evidence of distinctive features of mixed connective tissue disease.

A comparison of clinical, immunological and HLA-D region antigen features was made between 22 patients with mixed connective tissue disease (MCTD) and 118 patients with systemic lupus erythematosus (SLE), scleroderma or primary Sjögren's syndrome. The MCTD patients had hypergammaglobulinemia more often than did those with SLE and scleroderma, but had less skin ulceration, serositis, nephritis, central nervous system disease and hypocomplementemia than the SLE patients. The frequencies of HLA-DR4 and its Dw4 subtype were significantly increased in MCTD as compared with both the other patient groups and healthy controls. Anti-RNP antibodies and the clinical characteristics together seem to illustrate a disease syndrome which is clinically and genetically distinct and fits with the prevailing concept of MCTD.