Ankylosing spondylitis

Evidence of infectious cause

Sample PubMed cite1)

Rheumatology (Oxford). 2001 Jan;40(1):15-23. Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis.2)

Tiwana H, Natt RS, Benitez-Brito R, Shah S, Wilson C, Bridger S, Harbord M, Sarner M, Ebringer A. Division of Life Sciences, Infection and Immunity Group, King's College London, Stamford Street, London, UK. Abstract BACKGROUND: Increased levels of collagen types I, III and V are found in strictures of patients with Crohn's disease (CD) compared with normal gut tissue. Type IV collagen is present in the basement membranes, basal lamina, retina and cornea. Elevated levels of antibody to Klebsiella pneumoniae are found in both active CD and active ankylosing spondylitis (AS) patients compared with healthy controls. METHODS: Reactivities for immunoglobulin class-specific antibodies (IgM, IgG and IgA) against collagen types I, III, IV, V and whole K. pneumoniae were measured by ELISA in nine patients with early CD and 10 with late CD from King's College Hospital and 12 late CD patients and 36 HLA-B27-positive AS patients from Middlesex Hospital and was compared with values for 26 healthy controls from the Blood Transfusion Service in London. RESULTS: Levels of class-specific IgM, IgG and IgA antibodies to collagen types I, III, IV, V and K. pneumoniae were significantly elevated in early and late CD patients compared with healthy controls (P<0.001). Levels of IgM, IgG antibody to the four collagen types and K. pneumoniae were also significantly elevated (P<0.001) in AS patients compared with healthy controls. In addition, the level of IgA antibody to K. pneumoniae was elevated in AS patients (P<0.001). Furthermore, a positive correlation between antibody levels to collagen types I, III, IV and K. pneumoniae was demonstrated in both early and late CD patients and in those with AS, whilst a positive correlation to type V was found in early CD. CONCLUSION: The role of K. pneumoniae and anti-collagen antibodies in the aetiopathogenesis of CD and AS requires further study. PMID: 11157137

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Arthritis Rheum. 2009 Nov;60(11):3519-20; author reply 3520-1.

Time to prove the infective etiology of ankylosing spondylitis and related spondylarthritides: Comment on the article by Carter et al.3)

Zeidler H, Rihl M. Comment on: Arthritis Rheum. 2009 May;60(5):1311-6. PMID: 19877074

Time to prove the infective etiology of ankylosing spondylitis and related spondylarthritides: comment on the article by Carter et al To the Editor: We read with interest the recent article by Carter et al, which described an increased frequency of Chlamydia-positive synovial tissue samples, as determined by polymerase chain reaction (PCR), in patients with chronic undifferentiated spondylarthritis (uSpA) (1). This observation is a major step forward in elucidating the etiology of uSpA but is most likely also relevant for the whole spectrum of SpA. Currently, reactive arthritis is accepted as being associated with chlamydial infections and other enteric and sexually acquired infections. However, the causative role of microbes in ankylosing spondylitis (AS) is still a matter of debate, although urogenital tract infections and, more recently, Chlamydia trachomatis, have long been implicated as causative agents in AS.

As early as 1926, Visher (2) observed evidence of “osteoarthritis” in the spine or sacroiliac joints of 55% of young patients with chronic prostate infection. In 1953, Romanus reported signs of chronic prostatovesiculitis in 102 of 114 cases of AS (2). In 1960, these and other findings led to the suggestion that there is a true relationship between chronic urogenital tract infection and AS, even though the definite causal relationship has not been established (2). Later, Ford formulated the hypothesis that one agent may cause different clinical syndromes, and that a single syndrome may be attributable to many infectious agents (3). More recently, studies including patients with AS revealed an increased frequency of C trachomatis infection, as determined by investigation of the urogenital tract (4), and serologic analysis, including immunoblotting (5,6). Another study, however, in which screening for C trachomatis infection was performed using commercially available DNA amplification assays in urine specimens, did not reveal a higher prevalence in patients with AS compared with male control subjects in the same age group (7). In view of these conflicting findings, it would be of interest to learn more about Chlamydia-specific serologic testing and investigation of the urogenital tract in the patients with uSpA described by Carter et al.

The fact that AS may develop in patients with uSpA suggests that these entities share a common etiology. One study of patients with possible AS revealed a rate as high as 36% among patients in whom definite AS developed within a 10-year followup period (8). In addition, it was shown most recently that clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease (9). Fourteen of the patients (i.e., 88% of all patients with available radiographs) described by Carter et al had asymmetric grade 2 or grade 3 sacroiliitis at the time of study entry (1). Patients with unilateral grade 3 sacroiliitis fulfill the modified New York criteria for AS (10). Moreover, the clinical characteristics of the selected patients with uSpA have many signs and symptoms in common with reactive arthritis such as history (23%) or active keratoderma blennorrhagicum (15%) and history (13%) or active circinate balanitis (6%) (1). It would be of great interest to learn how many synovial tissue samples obtained from these patients were Chlamydia-positive, because chronic reactive arthritis may develop in patients with AS.

Furthermore, psoriatic arthritis (PsA) constitutes another candidate for investigations on the etiologic role of chlamydial infections. Silveira et al (11) performed a prospective study determining the prevalence of C trachomatis infection in patients with SpA, which demonstrated a significant frequency of positive urogenital C trachomatis culture (22%) as well as elevated levels of IgG antibodies (36%) or IgM antibodies (14%) against C trachomatis in patients with PsA. Using optimized PCR testing, we recently detected C trachomatis in synovial fluid samples from patients with PsA (12). Moreover, using the same PCR technique, we identified C trachomatis in the sacroiliac joint of a patient with PsA and human immunodeficiency virus infection who was HLA–B27– positive and had bilateral grade 2 sacroiliitis; this patient presented with acute posturethritis reactive arthritis and acute unilateral sacroiliitis, as determined by magnetic resonance imaging (13). Taken together, these findings indicate the possibility that C trachomatis is involved in the etiology of PsA in at least some patients.

In conclusion, it is time to determine definite proof of an infective, especially a chlamydial, etiology of AS and related SpA. Technologies are now available to enlarge the prevalent body of clinical, immunologic, and genetic studies. A concerted program of investigation by rheumatologists, microbiologists, and other researchers in the field is urgently needed. The chances to prove an infective etiology are higher than ever before.

Supported by the German Competence Network in Rheumatology, Berlin. Henning Zeidler, MD Markus Rihl, MD Hannover Medical School Hannover, Germany 1. Carter JD, Gerard HC, Espinoza LR, Ricca LR, Valeriano J, Snelgrove J, et al. Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis. Arthritis Rheum 2009;60:1311–6. 2. Ankylosing spondylitis and urogenital infection. Br Med J 1960;1: 865–6. 3. Ford DK. One syndrome: many infectious agents. J Rheumatol 1987;14:650–2. 4. Lange U, Teichmann J. Ankylosing spondylitis and genitourinary infection. Eur J Med Res 1999;4:1–7. 5. Csango PA, Upsahl MT, Romberg O, Kornstad L, Sarov I. Chlamydia trachomatis serology in ankylosing spondylitis. Clin Rheumatol 1987;6:384–90. 6. Kihlstrom E, Gronberg A, Bengtsson A. Immunoblot analysis of antibody response to Chlamydia trachomatis in patients with reactive arthritis and ankylosing spondylitis. Scand J Rheumatol 1989;18:377–83. 7. Van der Paardt M, van Denderen JC, van den Brule AJ, Morre SA, van der Horst-Bruinsma IE, Bezemer PD, et al. Prevalence of Chlamydia trachomatis in urine of male patients with ankylosing spondylitis is not increased. Ann Rheum Dis 2000;59:300–2. 8. Mau W, Zeidler H, Mau R, Majewski A, Freyschmidt J, Stangel W, et al. Clinical features and prognosis of patients with possible ankylosing spondylitis: results of a 10-year followup. J Rheumatol 1988;15:1109–14. 9. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 2009;60:717–27. 10. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984; 27:361–8. 11. Silveira LH, Gutierrez F, Scopelitis E, Cuellar ML, Citera G, Espinoza LR. Chlamydia-induced arthritis. Rheum Dis Clin North Am 1993;19:351–63. 12. Freise J, Bernau I, Meier S, Zeidler H, Kuipers JG. Optimized molecular biology testing for C. trachomatis in synovial fluid samples in clinical practice [submitted for publication]. 13. Rihl M, Wagner AD, Bakhsh KA, Rosenthal H, Bernateck M, Kohler L, et al. Detection of chlamydial DNA in the inflamed sacroiliac joint of a patient with multiple infections. J Clin Rheumatol 2009;15:195–7.


Vitamin D discovery outpaces FDA decision making.
Marshall TG
Bioessays30p173-82(2008 Feb)
Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis.
Tiwana H, Natt RS, Benitez-Brito R, Shah S, Wilson C, Bridger S, Harbord M, Sarner M, Ebringer A
Rheumatology (Oxford)40p15-23(2001 Jan)
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