Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment.

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

Clinical evaluation of the BioFire Respiratory Pathogen Panel for the guidance of empirical antimicrobial therapy in critically ill patients with hospital-acquired pneumonia: A multicenter, quality improvement project.

BACKGROUND: We aimed to determine whether implementing antimicrobial stewardship based on multiplex bacterial PCR examination of respiratory fluid can enhance outcomes of critically ill patients with hospital-acquired pneumonia (HAP). METHODS: We conducted a quality improvement study in two hospitals in France. Adult patients requiring invasive mechanical ventilation with a diagnosis of HAP were included. In the pre-intervention period (August 2019 to April 2020), antimicrobial therapy followed European guidelines. In the «intervention¼ phase (June 2020 to October 2021), treatment followed a multiplex PCR-guided protocol. The primary endpoint was a composite endpoint made of mortality on day 28, clinical cure between days 7 and 10, and duration of invasive mechanical ventilation on day 28. The primary outcome was analyzed with a DOOR strategy. RESULTS: A total of 443 patients were included in 3 ICUs from 2 hospitals (220 pre-intervention; 223 intervention). No difference in the ranking of the primary composite outcome was found (DOOR: 50.3%; 95%CI, 49.9%-50.8%). The number of invasive mechanical ventilation-free days at day 28 was 10.0 [0.0; 19.0] in the baseline period and 9.0 [0.0; 20.0] days during the intervention period (p = 0.95). The time-to-efficient antimicrobial treatment was 0.43 ± 1.29 days before versus 0.55 ± 1.13 days after the intervention (p = 0.56). CONCLUSION: Implementation of Rapid Multiplex PCR to guide empirical antimicrobial therapy for critically ill patients with HAP was not associated with better outcomes. However, adherence to stewardship was low, and the study may have had limited power to detect a clinically important difference.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer risk for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD risk, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability. In a cohort of 8,426 subjects with ASD and 169,804 controls with cognitive assessments, we found that rare coding CNVs and PRS-IQ increased ASD risk, even after adjusting for their effects on cognitive ability. Bottom decile PRS-IQ and CNVs both decreased cognitive ability but had opposing effects on ASD risk. Models combining both classes of variants showed that the effects of rare CNVs and PRS-IQ on ASD risk and cognitive ability were largely additive, further suggesting that risk for ASD is conferred independently from its effects on cognitive ability. Despite imparting mostly additive effects on ASD risk, rare CNVs and PRS-IQ showed opposing effects on core and associated features and developmental history among subjects with ASD. Our findings suggest that cognitive ability itself may not be the factor driving the underlying risk for ASD conferred by these two classes of genomic variants. In other words, ASD risk and cognitive ability may be two distinct manifestations of CNVs and PRS-IQ. This study also highlights the challenge of understanding how genetic risk for ASD maps onto its dimensional traits.

Potential Impact of Rapid Multiplex PCR on Antimicrobial Therapy Guidance for Ventilated Hospital-Acquired Pneumonia in Critically Ill Patients, A Prospective Observational Clinical and Economic Study.

Objectives: To investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP). Methods: Respiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio. Results: The predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy. Conclusions: Our results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.

Evaluation of the FilmArray® Pneumonia Plus Panel for Rapid Diagnosis of Hospital-Acquired Pneumonia in Intensive Care Unit Patients.

The FilmArray® Pneumonia plus Panel (FAPP) is a new multiplex molecular test for hospital-acquired pneumonia (HAP), which can rapidly detect 18 bacteria, 9 viruses, and 7 resistance genes. We aimed to compare the diagnosis performance of FAPP with conventional testing in 100 intensive care unit (ICU) patients who required mechanical ventilation, with clinically suspected HAP. A total of 237 samples [76 bronchoalveolar lavages (BALDS) and 82 endotracheal aspirates (ETADS) obtained at HAP diagnosis, and 79 ETA obtained during follow-up (ETATT)], were analyzed independently by routine microbiology testing and FAPP. 58 patients had paired BALDS and ETADS. The positivity thresholds of semi-quantified bacteria were 103-104 CFUs/mL or 104 copies/mL for BAL, and 105 CFUs/mL or copies/mL for ETA. Respiratory commensals (H. influenzae, S. aureus, E. coli, S. pneumoniae) were the most common pathogens. Discordant results for bacterial identification were observed in 33/76 (43.4%) BALDS and 36/82 (43.9%) ETADS, and in most cases, FAPP identified one supplemental bacteria (23/33 BALDS and 21/36 ETADS). An absence of growth, or polybacterial cultures, explained almost equally the majority of the non-detections in culture. No linear relationship was observed between bin and CFUs/mL variables. Concordant results between paired BALDS and ETADS were obtained in 46/58 (79.3%) patients with FAPP. One of the 17 resistance genes detected with FAPP (mecA/C and MREJ) was not confirmed by conventional testing. Overall, FAPP enhanced the positivity rate of diagnostic testing, with increased recognition of coinfections. Implementing this strategy may allow clinicians to make more timely and informed decisions.

Can power Doppler ultrasound of the entheses help in classifying recent axial spondyloarthritis? Data from the DESIR cohort.

Early diagnosis of axial spondyloarthritis (axSpA) remains a challenge due to the lack of specificity of clinical symptoms and variable prevalence of axial imaging findings permitting a definite diagnosis. Power Doppler ultrasonography (PDUS) of the entheses has demonstrated to be a potential useful tool for the classification and diagnostic management of early SpA independently of the phenotype. OBJECTIVES: To assess the classification value (sensitivity and specificity) of PDUS-defined enthesitis for identifying patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA (ASAS+) in patients with recent inflammatory back pain (IBP) (the DESIR (DEvenir des Spondylarthropathies Indifférenciées Récentes) cohort). METHODS: Baseline PDUS was performed at eight entheseal sites, and PDUS enthesitis was defined by the presence of vascularisation at entheseal insertion. RESULTS: 402 patients from the DESIR cohort underwent a PDUS evaluation. PDUS enthesitis was detected in 58 (14.4%) patients of whom 40 (14.2%) belonged to the ASAS+ patients and 18 (17%) to the ASAS- patients. The sensitivity of PDUS enthesitis was 13.9% and the specificity was 83.5%, with a positive predictive value of 69% and 26.8% of negative predictive value for meeting ASAS criteria for axSpA. Of the 18 ASAS- patients with positive PDUS, 59% fulfilled Amor's criteria, 88% European Spondyloarthropathy Study Group criteria and 59% both. CONCLUSIONS: In a cohort of patients with recent IBP, the prevalence of PDUS enthesitis was low (14.4%); however, its specificity for classifying patients as axSpA according to ASAS criteria was high (83.5%). PDUS enthesitis might be of additional value for classifying as patients with axSpA IBP who do not fulfil ASAS criteria.

Treatment strategies for psoriatic arthritis.

The therapeutic management of psoriatic arthritis has seen major changes over the last few years, as illustrated by the recent updates of the GRAPPA and EULAR recommendations. These changes were driven by new studies establishing important benefits from early management and tight control of disease activity. The concepts underlying the treatment of psoriatic arthritis must be reappraised in the light of these new data. The objectives of this review are to discuss new concepts, to describe and assess the new drug classes introduced for psoriatic arthritis and, whenever possible, to define the specific indications of each class based on the rheumatic disease phenotype and presence of extraarticular manifestations.

Early tumor necrosis factor α antagonist therapy in everyday practice for inflammatory back pain suggesting axial spondyloarthritis: results from a prospective multicenter french cohort.

OBJECTIVE: To determine the frequency of and factors associated with early tumor necrosis factor α (TNFα) antagonist therapy in everyday clinical practice in patients with suspected axial spondyloarthropathy (SpA). METHODS: We used data from the prospective observational study in the French Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; Outcome of Recent Undifferentiated Spondylarthropathies) cohort of 708 patients with recent-onset (<3 years) inflammatory back pain (IBP) suggesting axial SpA. TNFα antagonist use was recorded at months 6 and 12 and factors independently associated with TNFα antagonist therapy were identified by multivariate logistic regression. RESULTS: Among the 708 patients (mean age 33.8 years, 46.2% men), 166 (23.4%) patients received TNFα antagonist therapy by month 12, including 120 (73.6%) patients who fulfilled Assessment of SpondyloArthritis international Society (ASAS) axial criteria and 157 (94.6%) who fulfilled at least 1 SpA criteria set; 109 (65.6%) had no sacroiliitis. Factors independently associated with early TNFα antagonist therapy were high Ankylosing Spondylitis Disease Activity Score using the C-reactive protein level (odds ratio [OR]1-point increase 1.60, 95% confidence interval [95% CI] 1.25-2.03, P < 0.001), high physician's global disease activity score (OR 1.37, 95% CI 1.21-1.54, P < 0.001), ASAS nonsteroidal antiinflammatory drug score >50 (OR 1.88, 95% CI 1.24-2.87, P = 0.003), current or past disease-modifying antirheumatic drug use (OR 2.09, 95% CI 1.22-3.59, P = 0.008), systemic corticosteroid use (OR 2.48, 95% CI 1.43-4.34, P = 0.002), and mild to severe radiographic hip abnormalities (OR 9.43, 95% CI 2.11-42.09, P = 0.003). After adjustment on these factors, Achilles enthesis hypervascularization by power Doppler and number of work days missed were associated with TNFα antagonist therapy. CONCLUSION: In the DESIR cohort, approximately one-fourth of patients with recent IBP suggestive of axial SpA were under anti-TNFα therapy after 1 year of followup. All factors associated with this early initiation reflected higher disease activity, refractoriness, or severity, which suggests compliance of French rheumatologists with current treatment guidelines.

Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort.

OBJECTIVE: To assess whether factors such as inflammation by laboratory tests and MRI differ between early axial SpA with and without radiographic lesions. METHODS: Cross-sectional analysis of baseline data from Devenir des Spondylarthropathies Indifferenciées Récentes (DESIR) cohort patients having recent-onset inflammatory back pain and meeting Assessment of SpondyloArthritis international Society criteria. The baseline evaluation included radiographs and MRI of the SI joints (SIJs) and spine. Patients were classified as having radiographic lesions if they had at least one obvious sacroiliitis, grade 2 for at least one vertebral corner or grade 1 for at least two vertebral corners (at the cervical or lumbar level, according to the modified Stoke Ankylosing Spondylitis Spine Score). Associations between baseline characteristics and the presence of radiographic lesions were evaluated by estimating multi-adjusted odd ratios (aORs) and their 95% CIs using a logistic regression model. RESULTS: Of 475 patients, 180 (37.9%) had radiographic lesions. Factors positively associated with radiographic lesions were alcohol use (aOR 2.42; 95% CI 1.31, 4.44; P = 0.005), CRP level (aOR 1.44; 95% CI 1.13, 1.84; P = 0.003) and SIJ inflammation by MRI (aOR 2.25; 95% CI 1.40, 3.60; P = 0.001); negative associations occurred with good NSAID responsiveness (aOR 0.44; 95% CI 0.24, 0.81; P = 0.008); spinal MRI inflammation was associated with radiographic lesions only in smokers (aOR 1.99; 95% CI 1.01, 3.92; P = 0.048). CONCLUSION: Alcohol use, poor responsiveness to NSAIDs, CRP elevation, SIJ MRI inflammation and spinal MRI inflammation in smokers were independently associated with radiographic lesions in early axial SpA.

Does the site of magnetic resonance imaging abnormalities match the site of recent-onset inflammatory back pain? The DESIR cohort.

OBJECTIVES: To assess whether the site of axial pain (thoracic spine, lumbar spine or buttock(s)) was associated with the site of MRI lesions in patients with recent inflammatory back pain (IBP) suggesting spondyloarthritis. METHODS: We conducted a cross-sectional study of baseline data in 708 patients with recent IBP from the DESIR cohort. Radiographs of the sacroiliac joints (SIJs) and MRI scans of the SIJs and thoracic and lumbar spine were obtained routinely. Associations between pain sites and sites of inflammatory and structural MRI changes were evaluated using separate multivariate logistic regressions. RESULTS: Of the 648 patients with complete data, 61% had thoracic pain, 91.6% lumbar pain and 79.2% buttock pain. MRI inflammation was seen in 19%, 21% and 46% of patients at the thoracic, lumbar and SIJ sites, respectively. By multivariate analysis, pain was significantly associated with MRI inflammation only at the same site (adjusted OR (aOR)thoracic pain 1.71; 95% CI 1.09 to 2.67; p=0.02; aORlumbar pain 2.53; 95% CI 1.03 to 6.20; p=0.04; aORbuttock pain 2.86; 95% CI 1.84 to 4.46; p<0.0001). Pain site was not significantly associated with the site of structural MRI changes, except for buttock pain and SIJ structural MRI changes (aORbuttock pain 1.89; 95% CI 1.22 to 2.90; p=0.004). The association between pain site and site of MRI inflammation persisted in the subgroups with normal or doubtful SIJ radiographs or with Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis. CONCLUSIONS: The site of pain (thoracic spine, lumbar spine or buttock(s)) is associated with MRI inflammation at the same site in patients with recent IBP.

Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? A multicentre retrospective observational study.

INTRODUCTION: The aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis. METHODS: French rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires. RESULTS: Data were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy. CONCLUSION: In patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.

Long-term return to work after a functional restoration program for chronic low-back pain patients: a prospective study.

Low-back pain is a major health and socio economic problem. Functional restoration programs (FRP) have been developed to promote the socio-professional reintegration of patients with important work absenteeism. The aim of this study was to determine the long-term effectiveness of FRP in a group of 105 chronic low-back pain patients and to determine the predictive factors of return to work. One hundred-and-five chronic LBP patients with over 1 month of work absenteeism were included in a FRP. Pain, professional status, quality of life, functional disability, psychological impact, and fear and avoidance beliefs were evaluated at baseline, after 1 year and at the end of follow-up. Main effectiveness criterion was return to work. Fifty-five percent of the patients returned to work after mean follow-up time of 3.5 years, compared with 9% of the patients at work at baseline. Quality of life, functional disability, psychological factors, and fear and avoidance beliefs were all significantly improved. Three predictive factors were found: younger age at the onset of low-back pain, practice of sports, and shorter duration of sick leave at baseline. FRP show positive results in terms of return to work for chronic LBP patients with prolonged work absenteeism. Efforts should be made to propose such programs at an earlier stage of the disease.

Frequency and tolerance of antituberculosis treatment according to national guidelines for prevention of risk of tuberculosis due to tumor necrosis factor blocker treatment.

PURPOSE: Tumor necrosis factor (TNF) blockers increase the risk of tuberculosis infection. National recommendations in France for prevention of latent tuberculosis recommend treatment by rifampicin (RIF) 600 mg/day and isoniazid (INH) 300 mg/day for 3 months. However, its toxicity is unknown in this context and is a subject of debate. OBJECTIVE: To assess (a) frequency of prescription, (b) reasons for prescription, (c) tolerance of INH/RIF for prevention of tuberculosis. METHODS: Systematic retrospective study of medical records of one tertiary rheumatology unit, from 2002 to 2007, of all patients who were prescribed INH/RIF before receiving TNF blockers. DATA COLLECTION: patients'demographic characteristics, reasons of prescription, tolerance and levels of aminotransferase before and during INH/RIF treatment. ANALYSIS: Descriptive and determination of risk factors of hepatotoxicity by multivariate logistic regression. RESULTS: Of 1028 patients treated by TNF blockers between 2002 and 2007, 216 (21.1%) received INH/RIF treatment. Of 93 patients with complete data, 17 (18.2%) presented hepatotoxicity of which only one above 10 times the upper limit of the norm. Fourteen (15.0%) had other side effects. Ten (10.7%) patients had to interrupt INH/RIF for intolerance. Factors predicting intolerance were male sex, aminotransferases before treatment, a higher body mass index and leflunomide comedication. CONCLUSION: This systematic case review indicates a high rate of necessity for preventive treatment by INH/RIF, and in particular for positive skin tests. This association had a high rate of hepatotoxicity without severe consequences. A better screening of patients before preventive therapy is needed.

Dendritic cells from spondylarthritis-prone HLA-B27-transgenic rats display altered cytoskeletal dynamics, class II major histocompatibility complex expression, and viability.

OBJECTIVE: Spondylarthritis (SpA) is characterized by spinal and peripheral joint inflammation, frequently combined with extraarticular manifestations. Despite the well-established association of SpA with the class I major histocompatibility complex (MHC) allele HLA-B27, there are still different, parallel hypotheses on the relationship between HLA-B27 and disease mechanisms. The present study was undertaken to investigate several characteristics of mature dendritic cells (DCs), which are believed to be essential for triggering disease in a model of SpA in HLA-B27-transgenic rats. METHODS: We combined different whole-proteome approaches (2-dimensional polyacrylamide gel electrophoresis and iTRAQ) to define the most aberrant molecular processes occurring in spleen DCs. Videomicroscopy and flow cytometry were used to confirm both cytoskeletal and class II MHC expression deficiencies. RESULTS: Our proteome studies provided evidence of up-regulation of proteins involved in class I MHC loading, and unfolded protein response, along with a striking down-regulation of several cytoskeleton-reorganizing proteins. The latter result was corroborated by findings of deficient motility, altered morphology, and decreased immunologic synapse formation. Furthermore, class II MHC surface expression was reduced in DCs from B27-transgenic rats, and this could be linked to differences in class II MHC-induced apoptotic sensitivity. Finally, we found reduced viability of the CD103+CD4- DC subpopulation, which likely exerts tolerogenic function. CONCLUSION: Taken together, our findings have different important implications regarding the physiology of B27-transgenic rat DCs, which have a putative role in spontaneous disease in these rats. In particular, the reduced motility and viability of putatively tolerogenic CD4+ DCs could play an important role in initiating the inflammatory process, resulting in SpA.

Correlation between dendritic cell functional defect and spondylarthritis phenotypes in HLA-B27/HUMAN beta2-microglobulin-transgenic rat lines.

OBJECTIVE: To examine the functional capacity of dendritic cells (DCs) from a panel of HLA-B27/human beta2-microglobulin (Hubeta2m)-transgenic rat lines and crosses with varying susceptibilities to spondylarthritis (SpA)-like disease. METHODS: Mature splenic DCs were isolated from HLA-B27-transgenic, HLA-B7-transgenic, and/or Hubeta2m-transgenic rats and tested for support of allogeneic proliferation, compared with nontransgenic controls (all male rats on Lewis background). Graded numbers of DCs were cultured with allogeneic lymph node CD4+ T cells (dark agouti background). Proliferation was assayed by incorporation of tritiated deoxythymidine after 2-4 days of culture. RESULTS: Allogeneic proliferation stimulated by DCs from the healthy HLA-B27/Hubeta2m-transgenic line 21-3 and from the healthy Hubeta2m-transgenic line 283-2 was weakly decreased (21-3) or close to normal (283-2) as compared with that observed with control nontransgenic Lewis rat DCs. In contrast, the ability of DCs from (21-3 x 283-2)F1 rats, which develop a dramatic SpA phenotype, to stimulate allogeneic proliferation was markedly defective. When DC-induced allogeneic proliferation was compared among different transgenic lines and crosses with distinct levels of susceptibility to SpA-like disease, stimulatory capacity was inversely correlated with disease susceptibility. CONCLUSION: In HLA-B27/Hubeta2m-transgenic rats, a defective functional capacity of DCs correlates with susceptibility to SpA. Since it was previously demonstrated that defective DC function is not a consequence of disease, it could well be a principal factor in the spontaneous development of SpA in these lines.