The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.
In this population-based case-control study we linked nationwide histopathology data on 2,933 individuals with CD (Marsh stage 3; villous atrophy) to the Swedish Prescribed Drug Register to examine the association between use of systemic antibiotics and subsequent CD. We also examined the association between antibiotic use in 2,118 individuals with inflammation (Marsh 1-2) and in 620 individuals with normal mucosa (Marsh 0) but positive CD serology. All individuals undergoing biopsy were matched for age and sex with 28,262 controls from the population.
Antibiotic use was associated with CD (Odds ratio [OR]?=?1.40; 95% confidence interval [CI]?=?1.27-1.53), inflammation (OR?=?1.90; 95% CI?=?1.72-2.10) and normal mucosa with positive CD serology (OR?=?1.58; 95% CI?=?1.30-1.92). ORs for prior antibiotic use in CD were similar when we excluded antibiotic use in the last year (OR?=?1.30; 95% CI?=?1.08-1.56) or restricted to individuals without comorbidity (OR?=?1.30; 95% CI?=?1.16 - 1.46).
The positive association between antibiotic use and subsequent CD but also with lesions that may represent early CD suggests that intestinal dysbiosis may play a role in the pathogenesis of CD. However, non-causal explanations for this positive association cannot be excluded.
Autoantibodies against oxidatively modified low-density lipoproteins (oxLDL) and cardiolipin occur in patients with vascular diseases, including atherosclerosis. The ability of such antibodies to predict myocardial infarction (MI) was investigated in a prospective nested case-control study in which healthy 50-year-old men were followed up for 20 years. Raised levels of antibodies against oxLDL and cardiolipin at 50 years of age correlated positively with the incidence of MI and mortality related to MI 10 to 20 years later. IgG and IgA antibodies against cardiolipin were associated with MI between 50 to 60 years of age and IgG and IgA antibodies against oxLDL with MI at 60 to 70 years of age. Moreover, higher antibody levels were noted in those who died from acute MI in comparison to those who survived. The predictive power of IgA and IgG antibodies was strong and largely independent of that of other strong risk factors. In conclusion, raised levels of antibodies against oxLDL and cardiolipin may predict MI and MI-related death.
OBJECTIVE: To evaluate the prevalence and predictive value of anti-cyclic citrullinated peptide (anti-CCP) antibodies in individuals who subsequently developed rheumatoid arthritis (RA) and to determine the relationship to rheumatoid factor (RF) of any isotype. METHODS: A case-control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti-CCP antibody and RFs were determined using enzyme immunoassays. RESULTS: Eighty-three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1-4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti-CCP, 16.9% for IgG-RF, 19.3% for IgM-RF, and 33.7% for IgA-RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and
Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden.
Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.
To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors.
51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls.
The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives.
All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.
We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology/biochemistry, serology, and disease activity measures.
Immunoglobulin (Ig)M, IgG, and IgA levels against the DNA polymerase processivity factors of EBV, CMV, and HHV6, termed early antigen diffuse (EA/D), pp52, and p41, respectively, were determined in plasma samples from 77 SLE patients and 29 healthy controls by using enzyme-linked immunosorbent assays (ELISAs).
IgM, IgG, and IgA levels against EBV EA/D, and IgG and IgA levels against CMV pp52, were significantly higher in SLE patients compared with healthy controls. Furthermore, EBV EA/D- and CMV pp52-directed IgG levels were inversely and positively associated, respectively, with lymphocyte counts in SLE patients. None of the findings seemed to be associated with use of immunosuppressive medication.
Our results suggest strong, but opposite, associations of lytic EBV and CMV infections with SLE. The amplified humoral responses to EBV EA/D and CMV pp52 in our SLE patient cohort probably reflect aberrant control of EBV and CMV reactivation. However, reactivation of EBV appeared to correlate with lymphopenic manifestations in SLE patients whereas CMV reactivation seemed to correlate with increments in lymphocyte levels.
A pertussis outbreak was studied prospectively in an elementary school with 39 pupils. All had been immunized with at least three doses of Finnish diphtheria-tetanus toxoid-pertussis vaccine. Diagnosis of pertussis was based on culture, polymerase chain reaction results, and EIA serology using filamentous hemagglutinin (FHA), pertussis toxin, and 69-kDa outer membrane protein as antigens. At the first sampling, 21 children had symptoms suggestive of pertussis, and 18 were healthy. Of the latter, 8 remained healthy without any antibiotic treatment and 9 developed clinical pertussis 1-22 days later. One child developed cough later, but this symptom did not meet criteria for pertussis. The mean levels of IgG, IgM, and IgA antibodies to FHA were significantly higher in 8 healthy children than in 9 children who developed pertussis after the first sampling (P
Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.
The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case-control study.
The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay.
The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke.
The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.
Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogen Porphyromonas gingivalis may play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalis antibodies and ACPA.
Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinated peptide (anti-CCP2) isotypes and IgG anti-P. gingivalis lipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.
Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalis levels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) generally occurs in adults, especially in high-prevalence populations such as the Chinese and Eskimos. In Maghrebian populations, young patients affected with this malignancy represent 25% of the total NPC cases. In adults with NPC, relatively high titers of IgA antibodies to the EBV viral capsid antigen (VCA) and early antigen (EA) represent important markers. However, nearly 50% of young NPC patients are negative for IgA-anti-VCA and -EA or exhibit very low titers of these antibodies. We report here that 92% of sera from young NPC patients negative for IgA-EA and 89% of those negative for IgA-VCA were positive for IgG antibodies to the EBV transactivator protein (ZEBRA) at very high titers. Our results show that in young patients with NPC these antibodies represent the most reliable marker for diagnosis and prognosis, particularly when compared with conventional NPC markers, i.e., IgA-VCA (58%) and anti-EA (25%). The titers of IgG-ZEBRA antibodies increased along with lymph node involvement only in the young patient group, suggesting a prognostic value of this marker in this patient group.