The interrelationship between sex,susceptibility factors,and outcome in ankylosing spondylitis and its associated disorders including inflammatory bowel disease,psoriasis, and iritis

OBJECTIVE: To examine the evidence that families, where the mother has disease, carry more heritable factors and investigate the effect of maternal/paternal inheritance on phenotypic expression of disease in terms of (a) severity and outcome and (b) additional co-disorders. The children of women with ankylosing spondylitis (AS) develop the disease more often than the children of men. This suggests that either women with disease carry more susceptibility factors than men or that the uterine environment/breast feeding may play a role in AS. METHODS: The number of second degree relatives (i.e., grandparent, aunt/uncle) was calculated for those index patients with a mother with disease as opposed to a father. Outcome measures were compared and prevalence of secondary disorders (i.e., psoriasis, iritis, inflammatory bowel disease) was examined in patients with an AS mother as opposed to an AS father. RESULTS: The affected offspring of maternal cases had more second degree relatives with disease [20% vs 9%, respectively, p = 0.012, odds ratio (OR): 2.3, 95% confidence interval (CI): 1.2, 4.5] than did children of affected men. The affected children of a mother with AS were comparable in terms of disease activity, function, and radiology to children of a father with disease. Inflammatory bowel disease was more prevalent among children of AS mothers than AS fathers (15% vs 5%, respectively, p = 0.009, OR: 2.9, 95% CI: 1.3, 6.3). Psoriasis was less prevalent among sons of AS mothers than among sons of AS fathers (9% vs 22%, respectively, p = 0.03, OR: 0.4, 95% CI: 0.2, 0.9). CONCLUSION: The inherited susceptibility load is strongly linked to the sex of the parent with AS. Women with disease carry higher heritability (which is associated with inflammatory bowel disease) than do men. There is a male sex impact on susceptibility to psoriasis (when AS is present). However, there is no evidence that the susceptibility load has an effect on outcome or severity of disease (as measured by disease activity, function, and radiology), or that outcome is influenced by transmission of maternal as opposed to paternal factors.     

Incidence and prevalence of ankylosing spondylitis in Northern Norway

OBJECTIVE: To determine the incidence and prevalence of ankylosing spondylitis (AS) over a prolonged period in the 2 northernmost counties of Norway, where HLA-B27 has a high prevalence in the population. METHODS: We conducted a cohort study of all patients registered with a diagnosis of AS between 1960 and 1993 at the University Hospital of Northern Norway, which is the sole rheumatology department serving these counties. We registered demographics, year of disease onset (clinical disease), and year of diagnosis (radiograph confirmation) for all patients. The date of onset of clinical disease in patients with AS was used in the calculation of incidence rates. Annual incidence and point/period prevalence rates were expressed per 100,000 adults. Primary AS was defined as AS in the absence of psoriasis or inflammatory bowel disease (IBD). RESULTS: A total of 534 patients (75.1% male, mean age at clinical diagnosis 24.2 years, 93.0% HLA-B27 positive) had a confirmed diagnosis of AS (by the modified New York criteria). Median time from disease onset to radiologic confirmation was 8.0 years. Annual incidence of primary AS (n = 417) was 7.26, while estimated point prevalence rose from 0.036% in 1970 to 0.10% in 1980 and to 0.21% in 1990 with a period prevalence of 0.26%. AS was secondary to psoriasis or IBD in 117 patients (18.1%), with a diagnostic delay similar to that in primary AS. Annual incidence (14.1) and period prevalence in 1982-1993 (0.41%) were significantly higher in the town of Troms? than in the surrounding rural region (5.21 and 0.22%, respectively). Mortality in patients with AS was low. CONCLUSION: The incidence of AS was relatively stable in the northern part of Norway over a 34-year period. Incidence and prevalence are higher than reported in similar studies from Finland and Minnesota, possibly due to a higher population prevalence of HLA-B27.     

Evaluation of the comorbidity burden in patients with ankylosing spondylitis using a large US administrative claims data set

Comorbidities among US patients with ankylosing spondylitis (AS) are inadequately understood. This study compared the prevalence and incidence of comorbidities between patients with AS and matched controls using national claims databases. Adults enrolled in the MarketScan Commercial and Medicare databases with ≥?1 inpatient or ≥?2 non-rule-out outpatient diagnoses of AS between January 1, 2012 and December 31, 2014 were included. Patients had to have ≥?1 AS diagnosis in 2013; the first AS diagnosis in 2013 was assigned as the index date. Control patients without AS were matched to AS patients on age, geographic region, index calendar year, and sex. Comorbidities were evaluated in AS patients and matched controls during the baseline and follow-up periods (before and after the index date, respectively). Hazard ratios of developing new comorbidities were estimated using Cox proportional hazard models adjusted for patients’ characteristics. A total of 6679 patients with AS were matched to 19,951 control patients. In addition to extra-articular manifestations of AS (inflammatory bowel disease [IBD], psoriasis, uveitis), a higher proportion of AS patients had asthma, cardiovascular disease, depression, dyslipidemia, gastrointestinal ulcers, malignancies, multiple sclerosis, osteoporosis, sleep apnea, and spinal fractures during the baseline period than matched controls. After AS diagnosis, a higher proportion of patients developed newly diagnosed cases of cardiovascular diseases, depression, osteoporosis, spinal fracture, IBD, psoriasis, and uveitis than matched controls. In this real-world, US claims-based study, patients with AS were shown to have significantly more comorbidities than matched controls.     

Ankylosing spondylitis: interaction between genes, joints, age at onset, and disease expression.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disorder with symptom onset generally occurring in the late teens/mid-twenties. In women, a younger age at onset enhances disease susceptibility in the next generation. We examined the influence of age at symptom onset on phenotypic expression. METHODS: Patients were divided into cohorts according to age of symptom onset. The primary outcome measure was radiological progression (by Bath AS Radiology Index, BASRI). Secondary measures were disease activity (Bath AS Disease Activity Index, BASDAI), function (Bath AS Functional Index, BASFI), numbers undergoing AS related surgery, and percentage with secondary disorders. RESULTS: Age at onset had no significant effect on radiological progression (young onset vs late onset, 8.0, 8.6, respectively) disease activity (young vs late, 4.4, 4.4), need for non-hip surgical intervention (9%, 8%, respectively), or prevalence of secondary disorders (iritis, 40%, 41%; psoriasis, 20%, 19%; inflammatory bowel disease, 7.5%, 8.9%). By contrast, there was a striking increase in prevalence of total hip replacement in those with juvenile onset (18%, 8%, respectively; p < 0.001). Regardless of age at onset, spinal progression determined radiologically was greater in those with hip arthritis compared to those without (young onset hip involvement vs non-hip involvement, 9.7 (2.4), 7.2 (3.0) (p < 0.001); late onset hip involvement vs non-hip involvement, 10.1 (2.5), 7.1 (3.0), respectively]. Function deteriorates with age (young onset vs late onset, 3.7, 4.5, respectively; p < 0.01). CONCLUSION: (1) Hip disease (young or late onset) is a major prognostic marker for longterm severe disease (patients with hip disease have a spinal score increased by 2.5-3 points or 35-40% more change). (2) Hip involvement is more prevalent among patients with young age at onset. (3) Young onset patients without hip involvement do not have more severe disease. Thus, age at onset, itself, does not influence disease severity. (4) Since hip involvement and not age at onset is associated with worse outcome, patients with a young age at onset may be assumed to have an increased susceptibility load (i.e., genetic component or environmental trigger) rather than more severity genes. The lack of association between severity and age at onset implies that the determinants of susceptibility and severity are independent.     

Inflammatory bowel disease and ankylosing spondylitis associated with cutaneous vasculitis, glomerulonephritis, and circulating IgA immune complexes.

Two patients both with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) developed leucocytoclastic vasculitis of the skin and nephropathy. Immunofluorescence studies showed that there was perivascular deposition of immunoglobulin A in the skin biopsy specimens of both patients and in the renal mesangium of one patient. Serum samples of the two patients contained IgA immune complexes. The absence of previous reports on such a combination of symptoms in IBD or AS suggests that these patients may have a disease entity which is distinct from uncomplicated IBD or AS, and which may combine the immunopathological features of both underlying disorders.     

Prevalence of ankylosing spondylitis and other spondyloarthropathies among patients with inflammatory bowel disease: a population study (the IBSEN study)

OBJECTIVE: To study the occurrence of spondyloarthropathies (SpA) in patients with inflammatory bowel disease (IBD) seen 6 years after IBD diagnosis. METHODS: In a population based cohort of 654 patients with IBD, 521 patients (80%) were investigated, which included a complete rheumatological examination. Radiographs of the sacroiliac joints and lumbar spine were performed in 406 of these patients (78%). The development of SpA was analyzed with regard to the presence of HLA-B27, duration of IBD symptoms, and the extent of intestinal inflammation. RESULTS: The occurrence of ankylosing spondylitis (AS) was 2.6% in ulcerative colitis and 6% in Crohn's disease (p = 0.08), yielding an overall prevalence of 3.7% in IBD. No correlation between localization or extent of the intestinal inflammation and presence of AS was found. HLA-B27 was present in 73% of cases with AS. The overall prevalence of SpA was 22%. Inflammatory back pain without AS (IBP) was found in 18% of the patients. Typical features of SpA were rare, while fibromyalgia was common in IBP, indicating that IBP is not a precursor or manifestation of SpA in patients with IBD. The prevalence of radiological sacroiliitis without clinical features of SpA was 2.0%. CONCLUSION: AS occurred frequently in patients with newly diagnosed IBD. IBP did not seem to predispose to AS or other forms of SpA. The overall prevalence of SpA was 22%, whereas the prevalence of asymptomatic radiological sacroiliitis was low.     

Enteropathic spondyloarthropathy： A common genetic background with inflammatory bowel disease？

The association between spondyloarthropathy and inflammatory bowel disease （IBD） is largely established, although prevalence is variable because of different population selection and diagnostic methodologies. Most studies indicate that as many as 10%-15% of cases of IBD are complicated by ankylosing spondylitis （AS） or other forms of spondylarthritis （SPA）. Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronicity of articular complications. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonoscopy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time. The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among first- and second-degree relatives of affected AS or IBD patients and finally, the increased cross-risk ratios between AS and IBD, strongly suggest a shared genetic background. So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS. Although functional studies are still needed to better understand its pathogenic role, great effort is being spent therapeutically targeting this pathway that may prove effective for both disorders.     

The spondylitis of inflammatory bowel disease. Evidence for a non-HLA linked axial arthropathy

Of 12 patients with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) or sacroiliitis (SI), only 4 (32%) had HLA-B27. Family studies revealed 3 B27-negative relatives with AS, 1 with SI, 1 with SI and IBD, and 1 with IBD alone. HLA haplotypes did not segregate with disease. These data suggest a non-HLA linked genetic predisposition to IBD which also confers susceptibility to spondylitis, even in the absence of expression of bowel disease.     

A common genetic background for inflammatory bowel disease and ankylosing spondylitis: a genealogic study in Iceland

OBJECTIVE: Patients with ankylosing spondylitis (AS) and approximately 50% of their first-degree relatives may have a genetic abnormality that results in subclinical intestinal inflammation. This study was undertaken to examine the familial occurrence and cosegregation of AS and inflammatory bowel disease (IBD) in order to determine whether there is a shared genetic risk factor in families. METHODS: The Icelandic genealogy database and population-wide data on all living Icelanders diagnosed as having AS (n = 205) and/or IBD (n = 1,352) were used to estimate the risk ratios of AS for relatives of patients with AS, the risk ratios of IBD for relatives of patients with IBD, and the cross-risk ratios of AS for relatives of patients with IBD or of IBD for relatives of patients with AS. The mean kinship coefficients for each disease were calculated. The control population for disease risk calculations comprised 10,000-100,000 sets of matched Icelandic subjects. RESULTS: First-, second-, and third-degree relatives of patients with AS had risk ratios of 94, 25, and 3.5, respectively, indicating an increased risk of developing AS (each P < 0.0005), while first-, second-, and third-degree relatives of patients with IBD had risk ratios for IBD of 4.4, 2.2, and 1.4, respectively (each P < 0.0001). The cross-risk ratios of IBD were 3.0 and 2.1 in first- and second-degree relatives of patients with AS, respectively, and were the same for AS in first- and second-degree relatives of patients with IBD. With the exception of Crohn's disease, the risk of having AS, ulcerative colitis, or IBD in spouses of patients with these diseases did not differ significantly from that in controls. Calculation of the kinship coefficients confirmed these patterns of familial risk. CONCLUSION: Patients with AS or IBD in Iceland are significantly more related to each other than are randomly sampled control subjects, in terms of an increased risk of either or both conditions developing in third-degree relatives. These findings suggest that one or more undiscovered genetic variants may underlie the risk of both diseases.     

The spondylitis of inflammatory bowel disease

Of 12 patients with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) or sacroilitis (SI), only 4 (33%) had HLA-B27. Family studies revealed 3 B27- negative relatives with AS, 1 with SI, 1 with SI and IBD, and 1 with IBD alone. HLA haplotypes did not segregate with disease. These data suggest a non-HLA linked genetic predisposition to IBD which also confers susceptiblity to spondylitis, even in the absence of expression of bowel disease.     

Sacroiliitis – it’s not all B 27

Summary We describe an HLA-B27 positive patient in whom posttraumatic pyogenic sacroilitis led to complete unilateral sacroiliac joint ankylosis in the absence of any signs indicative of HLA-B27 associated spondyloarthropathy. Sacroiliitis is the pathologic hallmark – and usually one of the earliest pathologic manifestations – of ankylosing spondylitis (AS). Bilateral sacroiliitis is typical for ankylosing spondylitis. The frequency of asymmetric sacroiliitis may be higher in other inflammatory disorders, e.g., reactive arthritis, Reiters syndrome, spondylitis associated with psoriasis, or infammatory bowel disease. Most but not all of these disorders show an increased prevalence among individuals who have inherited the HLA-B27 gene. In the context of this case, we discuss the differential diagnosis of unilateral sacroiliitis. Received: 25 August 1998 Accepted: 11 May 1999     

Spondyloarthropathy is underestimated in inflammatory bowel disease: prevalence and HLA association

OBJECTIVE: To determine the overall prevalence of spondyloarthropathy (SpA) among patients with inflammatory bowel disease (IBD) [Crohn's disease (CD) and ulcerative colitis (UC)]. METHODS: One hundred three consecutive patients with IBD from a gastroenterology unit were questioned and examined for SpA symptoms. Patients previously diagnosed with SpA were excluded. All patients were questioned and examined for SpA symptoms such as inflammatory back pain, joint swelling, enthesitis, and psoriasis or a specific family history. Radiographs were taken of all sacroiliac joints. HLA loci A, B, C, and DR were determined in all patients. RESULTS: Thirty-nine percent of the patients with IBD had clinical articular manifestations: 30% had inflammatory back pain, 10% had synovitis, and 7% had a peripheral enthesopathy. The majority (90%) of patients with rheumatic complaints fulfilled the classification criteria for SpA and 10% fulfilled the criteria for ankylosing spondylitis. Asymptomatic sacroiliitis was found in an additional 18% of the patients. Moreover, sacroiliitis, symptomatic or asymptomatic, was related to the disease duration. HLA-B27 conferred an additional risk for inflammatory low back pain in patients with IBD. CONCLUSION: Articular involvement in IBD can be classified as SpA. The appearance of SpA occurs irrespective of the extent of the bowel disease. Moreover, asymptomatic sacroiliac involvement is a common manifestation in IBD and it is related to disease duration, suggesting evidence for a related pathogenic mechanism.     

Ankylosing spondylitis and bowel disease

Between 5 and 10% of cases of ankylosing spondylitis (AS) are associated with inflammatory bowel disease (IBD), either Crohn's disease or ulcerative colitis. A much larger percentage of AS patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The association with HLA-B27 is less strong in IBD-associated AS than in idiopathic AS, and there is evidence for an association between gut inflammation in AS with the Crohn's-disease-related CARD15 mutations. Despite the different genetics, the immunopathology suggests common inflammatory pathways in gut and joint inflammation in AS, and in gut inflammation in AS and IBD. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of AS patients by ileocolonoscopy is not indicated in the absence of gut symptomatology as only a small proportion of AS patients with subclinical gut inflammation will develop overt IBD over time. Treatment of AS associated with IBD with non-steroidal anti-inflammatory drugs (NSAIDs) is problematic because of concerns of potential re-activation of IBD by NSAIDs. Major advances have been made in recent years with the establishment of anti-tumour necrosis factor (TNF) therapy in AS, the other spondyloarthritides and IBD. Anti-TNF agents are of particular relevance to AS patients with concomitant IBD who are at risk of exacerbation of the underlying bowel disease when treated with NSAIDs. In IBD, infliximab, unlike etanercept, is effective in treating clinical symptoms, inducing and maintaining remission, and mucosal healing. Adalimumab appears to be effective in treating both AS and IBD; however, official approval is pending. Currently, infliximab is the drug of choice for the treatment of patients with active AS associated with IBD.     

Concepts and epidemiology of spondyloarthritis

The term 'spondyloarthritides' (SpA) comprises ankylosing spondylitis (AS), reactive arthritis, arthritis/spondylitis with inflammatory bowel disease, and arthritis/spondylitis with psoriasis. The main links between these diseases are an association with HLA-B27 and a similar clinical picture. Patients normally present with chronic low back pain or asymmetrical arthritis, predominantly of the lower limbs, and an overlap of these symptoms often occurs. AS is regarded as the most severe subtype. Recent attention has focused on earlier diagnosis of AS among patients with chronic low back, and this is becoming more important as effective therapies for early treatment have become available. AS is a disease of young people, normally starting in the third decade of life. The incidence and prevalence rates of AS, and of SpA as a whole, are strongly dependent and are directly correlated to the prevalence of HLA-B27 in a given population. Incidence rates of 0.5-8.2/100 000 population and prevalence rates of 0.2-1.2% have been described for AS, and about double these figures have been reported for SpA.     

Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment

Spondyloarthropathies(SpA) include many different forms of inflammatory arthritis and can affect the spine(axial SpA) and/or peripheral joints(peripheral SpA) with Ankylosing spondylitis(AS) being the prototype of the former. Extraarticular manifestations, like uveitis, psoriasis and inflammatory bowel disease(IBD) are frequently observed in the setting of SpA and are, in fact, part of the SpA classification criteria. Bowel involvement seems to be the most common of these manifestations. Clinically evident IBD is observed in 6%-14% of AS patients, which is significantly more frequent compared to the general population. Besides, it seems that silent microscopic gut inflammation, is evident in around 60% in AS patients. Interestingly, occurrence of IBD has been associated with AS disease activity. For peripheral SpA, two different forms have been proposed with diverse characteristics. Of note, SpA(axial or peripheral) is more commonly observed in Crohn's disease than in ulcerative colitis. The common pathogenetic mechanisms that explain the link between IBD and SpA are still ill-defined. The role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint("gut-joint" axis) has been recognized, in the context of a genetic background including associations with alleles inside or outside the human leukocyte antigen system. Various therapeutic modalities are available with monoclonal antibodies against tumour necrosis factor, interleukin-23 and interleukin-17, being the most effective. Both gastroenterologists and rheumatologists should be alert to identify the coexistence of these conditions and ideally follow-up these patients in combined clinics.     

Ankylosing spondylitis and inflammatory bowel disease. III. Clinical characteristics and results of histocompatibility typing (HLA B27) in 50 patients with both ankylosing spondylitis and inflammatory bowel disease.

A study was made, in co-operation with several gastroenterology and rheumatology centres, of the clinical and genetic characteristics (HLA B27) of 50 patients suffering from both inflammatory bowel disease (38 Crohn's disease (CD), 12 ulcerated colitis (UC)) and ankylosing spondylitis (AS), the latter diagnosis being established according to the New York criteria. 20 CD (52.6%) and 8 UC (66.7%) patients were HLA B27 positive. The presence of HLA B27 was studied in relation to clinical parameters, such as first occurrence of symptoms of AS or inflammatory bowel disease (IBD), a history of peripheral arthritis, iridocyclitis, and a positive history of AS or IBD. Our patients were found to have heterogeneous clinical features: on one side of the spectrum a group of cases was distingiushed with the typical characteristics of idiopathic AS, often being HLA B27 positive. On the other side a smaller group of HLA B27 negative patients was observed, with severe intestinal inflammatory pathology, lacking most of the typical clinical features of idiopathic AS ('secondary' form of AS). Finally, between these two extremes a group of patients was found with less pronounced clinical or genetic characteristics. These different clinical and histocompatibility patterns suggest a mixed aetiopathogenesis of AS in IBD patients. Such a 'syndrome' of AS might harbour both idiopathic AS and forms of AS 'secondary' to the intestinal inflammatory pathology.     

Prevalence of spondyloarthritis in Turkish patients with inflammatory bowel disease

Rheumatic manifestations are the most common extraintestinal findings of inflammatory bowel disease (IBD), although there are wide variations among different studies. The only previous Turkish study reported a rather high prevalence of spondyloarthritis (SpA) in patients with IBD. We aimed to determine the frequency of SpA and ankylosing spondylitis (AS) in patients with IBD attending a gastroenterology clinic from a referral centre. The study was conducted in 122 patients with established diagnosis of IBD [28 with Crohn’s disease (CD) and 94 with ulcerative colitis (UC)]. A detailed medical history was obtained and a complete physical examination was performed in all the patients. Standard pelvic X-rays for examination of the sacroiliac joints were performed only when clinically indicated. The X-rays were read blindly by an experienced rheumatologist and reported according to the established grading system. The modified New York criteria were used to classify AS, and the European Spondyloarthropathy Study Group criteria for SpA. The prevalence of AS and SpA in patients with IBD was 8.2 and 28.7%, respectively. SpA was found to be significantly more common in the patients with CD compared to patients with UC, but the frequency of AS was not different between these two groups. There was no correlation between localisation or extent of the intestinal inflammation and presence of AS and SpA. A higher frequency of women was observed in patients diagnosed as SpA. Almost half of the patients with SpA (45.7%) had not been diagnosed before the study, although they had a history of IBP and/or peripheral arthritis. This study suggests that the prevalences of SpA and AS in Turkish patients with IBD are similar to those in many other populations. There may be a significant female predominance of SpA among patients with IBD.     

Comparison of osteitis condensans ilii and ankylosing spondylitis in female patients: clinical, radiological and HLA typing characteristics

A study comparing 12 patients with ankylosing spondylitis (AS) to 25 with osteitis condensans ilii (OCI), referred to a rheumatic disease center, was carried out to determine whether OCI represents a varient of AS in women. In the group with OCI, chronic lumbodorsal pain was present in 9, 36%, a 'fibrositis' syndrome in 6, 24%, and 16, 64% had recurrent episodes of polyarthralgia. A definite arthritis with effusion developed in 10 patients, 40%. No patient with OCI had iritis or colitis, whereas 4 patients with AS had iritis and four had colitis. Radiographs of the spine showed no evidence of spondylitis in the OCI group. Of the 25 patients with OCI, only 2, 8% were HLA B27 positive compared with 11 of 12 patients with AS, 92%. These results suggest that OCI is not a variant of AS in women.     

Concordance of disease severity among family members with ankylosing spondylitis?

OBJECTIVE: The heritability of disease activity and function in ankylosing spondylitis (AS) have been estimated at 0.51 and 0.63 (i.e., 51% and 63%), respectively. We examined the concordance of disease severity among family members in terms of disease activity, function, radiological change, prevalence of iritis, and juvenile onset. METHODS: Disease activity and functional impairment due to AS were studied using the Bath AS Disease Activity Index (BASDAI) and Functional Index (BASFI) self-administered questionnaires; radiographic involvement was measured using the Bath AS Radiology Index (BASRI) scale. Familial correlation of BASDAI and BASFI was assessed in 406 families with 2 or more cases, using the program PAP. Parent-child and sibling-sibling concordance for iritis and juvenile AS were also studied in these families. Heritability of radiological disease severity based on the BASRI was assessed in 29 families containing 60 affected individuals using the program SOLAR. RESULTS: Correlations between parent-child pairs for disease activity and function were 0.07 for both. Correlations between sibling pairs for disease activity and function were 0.27 and 0.36, respectively. The children of AS parents with iritis were more likely to develop iritis [27/71 (38%)] than children of non-iritis AS parents [13/70 (19%)] (p = 0.01). Parents with JAS were more likely to have children with JAS [17/30 (57%) compared to non-JAS parents 34/111 (30%)] (p = 0.002). The heritability of radiological disease severity based on the BASRI was 0.62. CONCLUSION: While correlation in severity between parent and child is poor, siblings do resemble each other in terms of severity, supporting the findings of segregation studies indicating significant genetic dominance in the heritable component of disease activity. Significant parent-child concordance for iritis and juvenile disease onset suggest that there are genetic risk factors for these traits independent of those determining the risk of AS itself. The finding of significant heritability of radiological change (BASRI) provides support using an objective measure for the observed heritability of the questionnaire-assessed disease severity scores, BASDAI and BASFI.     

Polymorphonuclear leucocyte motility in men with ankylosing spondylitis.

The polymorphonuclear leucocyte (PMN) response to a chemotactic or chemokinetic stimulus is enhanced in men with ankylosing spondylitis (AS). This effect does not parallel the severity of disease activity or the size of the acute phase response, and it is independent of non-steroidal anti-inflammatory drug treatment. Polymorph function is normal in HLA-B27 positive brothers of probands with AS and in other HLA-B27 positive individuals in the absence of disease. Polymorph motility is also normal in patients with psoriasis vulgaris or Crohn's disease, indicating that enhanced PMN motility is not a non-specific consequence of all inflammatory disorders.