Claus Bo Svendsen

Heredity in sarcoidosis: a registry-based twin study.

Background: Sarcoidosis is a multiorgan granulomatous inflammatory disease of unknown aetiology. Familial clustering of cases and ethnic variation in the epidemiology suggests a genetic influence on susceptibility to the disease. This paper reports twin concordance and heritability estimates of sarcoidosis in order to assess the overall contribution of genetic factors to the disease susceptibility. Methods: Monozygotic and dizygotic twins enrolled in the Danish and the Finnish population-based national twin cohorts (61 662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland registry of reimbursed medication using the 8th and 10th editions of the International Classification of Diseases. The Fisher exact test was used to compare probandwise concordance rates in different zygosity groups. Heritability was estimated based on a multifactorial threshold liability model. Results: A total of 210 twin pairs with at least one proband with a diagnosis of sarcoidosis were identified. The probandwise concordance rate was higher in monozygotic than in dizygotic twins (0.148 vs 0.012). Compared with the general population there was an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was only 7-fold. Aetiological model fitting gave a heritability of sarcoidosis of 0.66 (95% CI 0.45 to 0.80). Conclusions: This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis. This result should encourage the search for molecular genetic markers of susceptibility to the disease.

Seasonal and habitat variation in the prevalence of Rickettsia helvetica in Ixodes ricinus ticks from Denmark.

A total of 704 unfed ticks of the species Ixodes ricinus collected in Denmark were screened for Rickettsia DNA by a genus-specific real-time PCR. Of the nymphs, 4.7% (31/662) were positive for rickettsial DNA. Among the positive ticks, we observed a seasonal and habitat variation. The infection rate was highest in May as compared to July, August, and October. Ecotone (high tick density) showed an elevated prevalence as compared to spruce or beech forests. Sequencing revealed only DNA from R. helvetica.

The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis

Background:  The butyrophilin‐like 2 (BTNL2) gene is located on chromosome 6p21.3 close to the HLA‐class II genes. An association has been reported between sarcoidosis and a single nucleotide polymorphism in BTNL2, rs2076530, also termed the A allele.

Detection of Rickettsia spp. in Danish ticks (Acari: Ixodes ricinus) using real-time PCR.

We examined 192 Ixodes ricinus tick nymphs from Denmark for the presence of Rickettsia spp. We used a species-specific real-time PCR; 13.0% of the ticks were positive for rickettsial DNA. Only DNA from Rickettsia helvetica was found in the ticks.

Quantiferon test for tuberculosis screening in sarcoidosis patients

Abstract Background: Tumour necrosis factor-alpha (TNF-α) inhibitors have been introduced in the treatment of refractory sarcoidosis. These biologics may reactivate latent tuberculosis infection (LTBI). Despite its known limitations, the tuberculin skin test (TST) is currently used for the diagnosis of LTBI in Danish sarcoidosis patients. We report the results of a screening using the interferon-gamma release assay (IGRA) QuantiFERON TB Gold (QFN) for the diagnosis of LTBI. We aimed to assess whether the QFN is reliable for diagnosing LTBI among sarcoidosis patients and if results are influenced by disease activity or immunosuppressive treatment. Methods: A prospective study was performed from 2005 to 2007 among sarcoidosis patients who were candidates for TNF-α inhibitor treatment. Information on immunosuppressive treatment was obtained from the medical records. Disease activity was assessed by biochemistry, chest roentgenograms and pulmonary function tests. The predictive value of QFN results was evaluated by follow-up in the Danish National Tuberculosis Registry. Results: A total of 44 sarcoidosis patients (22 men) with a median age of 39 y (range 25–59 y) were enrolled; 93% had a negative QFN test result and 7% had an indeterminate result. Forty-three percent had disease activity and 57% (n = 25) received immunosuppressive treatment. There was no significant difference in QFN interferon-γ response between subjects with or without disease activity (p > 0.4) and between treated vs non-treated patients (p > 0.5). At follow-up using the Danish tuberculosis registry, there was no occurrence of tuberculosis among study participants. Conclusions: The predictive value of the QFN seems good among Danish sarcoidosis patients and the results appear to be unaffected by sarcoidosis disease activity and immunosuppressive treatment.

A novel fluorescent in situ hybridization technique for detection of Rickettsia spp. in archival samples.

A novel, sensitive and specific method for detecting Rickettsia spp. in archival samples is described. The method involves the use of fluorescently marked oligonucleotide probes for in situ hybridization. Specific hybridization of Rickettsia was found without problems of cross-reactions with bacterial species shown to cross-react serologically.

Determination of rickettsial and antinuclear antibodies in Danish patients with sarcoidosis.

Introduction:  Rickettsia helvetica has been proposed as an aetiological agent in sarcoidosis.

Is sarcoidosis a rickettsiosis? An archival study

Abstract Background: Based on earlier research, Rickettsia helvetica could possibly be involved in the pathogenesis of sarcoidosis. Rickettsiae are transmitted to humans by a tick vector, Ixodes ricinus; this tick is highly prevalent in Northern Europe. We aimed to investigate the association between evidence of rickettsiae and sarcoidosis in histological samples. Methods: We included formalin-fixed, paraffin-embedded mediastinal lymph node biopsies from 52 ethnic Danish patients with sarcoidosis and compared these with 50 biopsies from ethnic Danish patients with mediastinal lymphadenopathy of other causes. Samples were analysed for: (1) rickettsial DNA by real-time polymerase chain reaction (PCR) and (2) rickettsial rDNA (ribosomal DNA) by a specific fluorescence in situ hybridization technique (FISH). Results: Rickettsia was not detected in biopsies by real-time PCR and/or FISH analyses. Conclusion: Our results do not support the hypothesis that Rickettsia is involved in the pathogenesis of sarcoidosis.

The continuing search for Mycobacterium tuberculosis involvement in sarcoidosis: a study on archival biopsy specimens

Introduction:  Increasing evidence indicates that mycobacteria may be involved in the aetiology and pathophysiology of sarcoidosis.

Comparison of two commercially available ELISA antibody test kits for detection of human antibodies against Coxiella burnetii

Background: Q fever is a zoonosis caused by Coxiella burnetii. The disease is emerging in many parts of the world, likely in part due to increased awareness and the availability of better diagnostic tests. The clinical diagnosis of Q fever is difficult, and most confirmed cases rely on serology. Methods: This study compared the sensitivity, specificity, and performance of 2 commercial enzyme-linked immunosorbent assay (ELISA) kits, with a commercial microimmunofluorescence antibody test (IFA) used as reference. Results: One of the ELISA kits showed a higher sensitivity and a lower cross-reactivity than the other kit. Likewise, the same kit was superior when comparing the area under the receiver operating characteristic curves. Conclusions: The results support the continued use of IFA as a primary serological test for Q fever; for large numbers of samples, an ELISA kit can be used as a screening tool, if followed by a confirmatory IFA test.