Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement.

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.

Effects of vertebral fusion on levels of pro-inflammatory and catabolic mediators in a rabbit model of intervertebral disc degeneration.

OBJECTIVE: The aim of this study was to explore the alterations in levels of pro-inflammatory and catabolic mediators following vertebral fusion in a rabbit model of intervertebral disc degeneration. METHODS: In this study, 24 female New Zealand albino rabbits (aged 4 to 5 months and weighing 3 to 3.5 kg) were used. All the animals were randomly categorized into four groups, and dorsal spinal exposure of all lumbar vertebrae was routinely performed in each group. While disc degeneration was created in groups B, C, and D, spinal fusion was added to disc degeneration in groups C and D. Disc degeneration was typically created by puncturing the discs with an 18-gauge needle under the guidance of C-arm imaging. Fusion was achieved with posterior/posterolateral decortication and iliac bone grafts. The rabbits in groups A, B, and C were euthanized, and the discs were removed in the first week after the surgery. The rabbits in Group D were sacrificed, and the discs were harvested at 5 weeks after the surgery. The levels of Interleukin (IL)-1ß, IL-6, Nitric Oxide (NO), Matrix Metalloproteinase (MMP)-3, MMP-13, and Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in the discs were analyzed using enzyme-linked immunosorbent assay kits. RESULTS: Significant increase was observed in the protein levels of both pro-inflammatory and catabolic mediators in disc degeneration groups (Group B, C, and D) compared to Group A. In the fusion groups (Group C and D), these increased mediators decreased, compared to non-fusion group (Group B), (IL1-ß P = 0.017, TIMP-1 P = 0.03, NO P = 0.03). However, there was no statistically significant difference in mediator levels between the short- and long-term fusion (Group C versus D). CONCLUSION: The results of this study have shown that a significant decrease in pro-inflammatory and catabolic mediators may be expected after vertebral fusion whereas there may be no significant difference between the first and fourth week of fusion surgery. These findings may contribute to clarifying the mechanism of action of vertebral fusion in the treatment of low back pain.

Collision Lesions of Calcifying Pseudoneoplasm of the Neuraxis and Rheumatoid Nodules: A Case Report With New Pathogenic Insights.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.

Inflammatory mediators and the risk of falls among older women with acute low back pain: data from Back Complaints in the Elders (BACE)-Brazil.

PURPOSE: To investigate the association between plasma levels of inflammatory cytokines (interleukin [IL]-1-ß, IL-6, tumor necrosis factor [TNF]-α, and the soluble TNF receptor 1 [sTNF-R1]), disability, and risk of falls in older women with acute low back pain (LBP). METHODS: This cross-sectional study comprised a subsample of older women from the Back Complaints in the Elders international cohort study. Plasma levels of IL-1-ß, IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays. Pain was assessed using the Numerical Pain Scale and McGill Pain Questionnaire, while disability was measured using the Roland Morris Questionnaire and gait speed. Risk of falls was estimated using the Physiological Profile Assessment. Linear regression model was used to verify the association between independent variables and fall risk. RESULTS: One hundred and ten women (aged 69.97 ± 5.5 years) with acute LBP were included. The regression model showed an association between the risk of falls and IL-6 levels, pain, gait speed, and years of education. It also explained 21.2% of risk of falls variance. The model equation was: fall risk = 1.28 + (0.19 IL-6) + (0.02 quality of pain) + (- 0.71 gait speed) + (-0 .17 educational level). CONCLUSIONS: This study showed an association between risk of falls and IL-6, pain, gait speed, and educational level in older women with LBP. These slides can be retrieved under Electronic Supplementary Material.

Effects of photobiomodulation therapy on inflammatory mediators in patients with chronic non-specific low back pain: Protocol for a randomized placebo-controlled trial.

INTRODUCTION: Low back pain (LBP) is ranked as one of the most prevalent health conditions. It is likely that some inflammatory mediators could be associated with pain and disability in these patients. Photobiomodulation therapy (PBMT) is a non-pharmacological therapy often used in patients with LBP and one of the possible mechanisms of action of therapy is modulate inflammatory mediators. However, to date there are no studies that evaluated the effects of PBMT on the levels of inflammatory mediators in patients with LBP. The aim of this study is to evaluate the acute effects of PBMT on systemic levels of inflammatory mediators and pain intensity in patients with chronic non-specific low back pain. METHODS AND ANALYSIS: This is a prospectively registered, two-arm randomized placebo-controlled trial with blinded patients, assessors and therapists. Eighteen patients with chronic non-specific LBP will be randomized into 2 groups: placebo or active PBMT. The treatment will be provided in a single session. The primary outcome will be levels of prostaglandin E2 (PGE2). The secondary outcomes will be levels of necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and pain intensity. Biochemical and clinical outcomes will be measured at baseline and 15 minutes after the single treatment session. DISCUSSION: Despite PBMT be used in musculoskeletal disorders such as LBP, to the best of our knowledge this is the first study that will investigate a possible biological mechanism behind the positive clinical effects of PBMT on non-specific chronic low back pain. ETHICS AND DISSEMINATION: The study was approved by the Regional Research Ethics Committee. The results will be disseminated through publication in peer-reviewed international journal and conferences. TRIAL REGISTRATION NUMBER: NCT03859505.

Propionibacterium acnes induces discogenic low back pain via stimulating nucleus pulposus cells to secrete pro-algesic factor of IL-8/CINC-1 through TLR2-NF-κB p65 pathway.

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.

Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway.

Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 µg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.

Mast Cell-Intervertebral disc cell interactions regulate inflammation, catabolism and angiogenesis in Discogenic Back Pain.

Low back pain (LBP) is a widespread debilitating disorder of significant socio-economic importance and intervertebral disc (IVD) degeneration has been implicated in its pathogenesis. Despite its high prevalence the underlying causes of LBP and IVD degeneration are not well understood. Recent work in musculoskeletal degenerative diseases such as osteoarthritis have revealed a critical role for immune cells, specifically mast cells in their pathophysiology, eluding to a potential role for these cells in the pathogenesis of IVD degeneration. This study sought to characterize the presence and role of mast cells within the IVD, specifically, mast cell-IVD cell interactions using immunohistochemistry and 3D in-vitro cell culture methods. Mast cells were upregulated in painful human IVD tissue and induced an inflammatory, catabolic and pro-angiogenic phenotype in bovine nucleus pulposus and cartilage endplate cells at the gene level. Healthy bovine annulus fibrosus cells, however, demonstrated a protective role against key inflammatory (IL-1ß and TNFα) and pro-angiogenic (VEGFA) genes expressed by mast cells, and mitigated neo-angiogenesis formation in vitro. In conclusion, mast cells can infiltrate and elicit a degenerate phenotype in IVD cells, enhancing key disease processes that characterize the degenerate IVD, making them a potential therapeutic target for LBP.

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid.

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, although >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying nonpainful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy control participants, subjects with nonpainful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (eg, cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (eg, hemopexin). Cystatin C and hemopexin were selected for further examination using enzyme-linked immunosorbent assay in a larger cohort. While cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability, and DD severity. This study shows that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP. PERSPECTIVE: CSF was examined for differential protein expression in healthy control participants, pain-free adults with asymptomatic intervertebral DD, and LBP patients with painful intervertebral DD. While DD was related to inflammation regardless of pain status, painful degeneration was associated with markers linked to nerve injury.

Characterization of degenerative human facet joints and facet joint capsular tissues.

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.

SIRT1-related inhibition of pro-inflammatory responses and oxidative stress are involved in the mechanism of nonspecific low back pain relief after exercise through modulation of Toll-like receptor 4.

Low back pain is a common clinical problem that causes disability and impaired quality of life. While the reason behind low back pain was largely considered to be of musculoskeletal origin, the contribution of inflammatory cytokines and oxidative stress could never be overlooked. Exercise has been proven to be an effective approach to treat low back pain. However, the mechanism of the exercise effect on the inflammatory cytokines and oxidative stress is still largely unknown. In this study, we revealed that exercise intervention reduces Toll-like receptor 4 (TLR-4) pathway and enhances Sirtuin 1 (SIRT1) expression in low back pain patients. We also confirmed that exercise up-regulates the expression of peroxisome proliferator-activated receptor-gamma, PPAR-γ coactivator-1 and FoxOs family proteins and also increases the activity of catalase and superoxide dismutase in patients with low back pain. Furthermore, we found that exercise intervention attenuates the oxidative stress, pro-inflammatory cytokine concentrations and p53 expression in patients with low back pain. This study demonstrates that exercise intervention improves low back pain symptoms through regulation of the SIRT1 axis with repression of oxidative stress and TLR-4 inhibition.

Th17 cell frequency and IL-17 concentration correlate with pre- and postoperative pain sensation in patients with intervertebral disk degeneration.

Numerous studies have revealed the presence of T helper 17 (Th17) cells in pathologic intervertebral disk (IVD) tissues and the contribution of Th17-associated cytokines to the development of this disease. However, the pre- and postoperative changes in the proportion of Th17 cells and the concentration of IL-17 in the peripheral blood of patients with IVD degeneration are not clear. The levels of Th17 frequency and the interleukin-17 (IL-17) concentration in peripheral blood from patients and volunteers were examined by flow cytometry and by enzyme-linked immunosorbent assay (ELISA), respectively. The clinical results were evaluated using the visual analogue scale (VAS). These results were subjected to a correlation analysis. Compared with the normal controls, the proportion of Th17 cells and the concentration of IL-17 were significantly increased preoperatively in patients with IVD degeneration. Postoperatively, the levels of Th17 cells and the expression of IL-17 were dramatically decreased. The correlation analysis of the VAS pain scores, Th17 cell frequency, and IL-17 concentration, including the pre- and postoperative levels and the changes induced by the surgery, revealed a positive correlation. The authors' results explain the contribution of Th17 cells and IL-17 to the pain sensation experienced by patients with IVD degeneration. These 2 factors may be good indicators for the evaluation of the surgical outcome of patients with lumbar disk herniation.

Generation of a high-fidelity antibody against nerve growth factor using library scanning mutagenesis and validation with structures of the initial and optimized Fab-antigen complexes.

Nerve growth factor (NGF) is indispensable during normal embryonic development and critical for the amplification of pain signals in adults. Intervention in NGF signaling holds promise for the alleviation of pain resulting from human diseases such as osteoarthritis, cancer and chronic lower back disorders. We developed a fast, high-fidelity method to convert a hybridoma-derived NGF-targeted mouse antibody into a clinical candidate. This method, termed Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. Functional and structural comparisons between tanezumab and the mouse 911 precursor antibody using neurotrophin-specific cell survival assays and X-ray crystal structures of both Fab-antigen complexes illustrated high fidelity retention of the NGF epitope. These results suggest the potential for wide applicability of the LSM method for optimization of well-characterized antibodies during humanization.

Association between baseline IL-6 and 1-year recovery in lumbar radicular pain.

BACKGROUND: In the present study, the influence of cytokines on 1-year recovery in lumbar radicular pain was examined. METHODS: In total, 110 patients with symptomatic lumbar disc herniation were followed for 1 year. Uni- and multivariate linear regression was used to assess the influence of interleukin (IL)-6, IL-8, disc degeneration and endplate changes (Modic changes) on the changes in the Oswestry Disability Index (ODI change; primary outcome) and visual analogue scale (VAS) for low back pain (LBP) and leg pain (secondary outcomes). RESULTS: Less favourable ODI outcome correlated with higher serum IL-6 levels (B = -3.41, 95% CI -5.52 to -1.30, p = 0.002), non-surgical treatment (B = -7.03, 95% CI 1.21 to 12.84, p = 0.018), higher baseline back pain intensity (B = -2.28, 95% CI -3.21 to -1.35, p < 0.001) and low educational level (B = -5.57, 95% CI 0.66 to 10.47, p = 0.027). High VAS for LBP and leg pain at 1 year was associated with high levels of serum IL-6, higher back pain intensity and longer duration of lumbar radicular pain at baseline. CONCLUSIONS: High serum IL-6 levels, but not disc degeneration or Modic changes, were associated with less favourable recovery in patients with lumbar radicular pain. Intense initial back pain, non-surgical treatment, lower educational level and longer duration of radicular pain before treatment also correlated with a slower recovery the first year after disc herniation.

Molecular immunotherapy might shed a light on the treatment strategies for disc degeneration and herniation.

Despite surgical discectomy is one of the most effective treatments for intervertebral disc degeneration and lumbar disc herniation, a number of patients still complain of reserved low back pain, sciatica and numbness post-operatively with decreased life quality. Sciatica in patients with disc herniation is not only due to mechanical compression from herniated nucleus pulposus, but chemical and immunity agents. The intervertebral disc is composed of annulus fibrosus in the wedge and gelatinous nucleus pulposus in the centre with cartilage endplate sandwiched. Similar to other immune privilege organs, human intervertebral disc is one of the biggest avascular structures with FasL expression. Moreover, FasL-Fas and TRAIL death pathways might play roles in the machinery of immune privilege of the disc. We found that down-regulated miR-155 promotes Fas-mediated apoptosis in disc degeneration. Furthermore, once exposed to human immune system, nucleus pulposus can activate multiple specific and non-specific immune responses with cellular and fluid immune cells and molecules involved. Taken together, we hypothesize that a combined molecular immunotherapy with local and systemic immunity regulators might shed a novel light on the treatment strategies for disc degeneration and herniation.

Th17 lymphocyte levels are higher in patients with ruptured than non-ruptured lumbar discs, and are correlated with pain intensity.

BACKGROUND: Th17 lymphocytes have important roles in inflammation and autoimmune disease. Research on relationship between Th17 lymphocytes and pain associated with lumbar disc herniation (LDH) is limited. The purpose of this study was to examine the association of pain and Th17 lymphocyte and interleukin (IL)-17 levels in patients with herniated and non-herniated lumbar discs. METHODS: Thirty-four patients with single lumbar intervertebral disc herniation (median age, 44 years), and 17 healthy adults (median age, 37 years) were enrolled. Patients were divided into 2 groups depending on their magnetic resonance imaging (MRI) results and visual observations during surgery (group P, non-ruptured disc, n=15; group E, ruptured disc, n=19). Patients received posterior or transforaminal lumbar interbody fusion. Preoperative pain intensity was recorded using a visual analogue scale (VAS) score. The percentage of Th17 lymphocytes and IL-17 and prostaglandin E2 (PGE2) levels in peripheral blood were determined. Disc tissue was examined by immunohistochemistry for Th17 and IL-17 expression. RESULTS: Preoperative VAS pain scores were significantly higher in group E than group P (8.32±1.04 vs. 6.33±2.68, respectively, p=0.009). Similarly, PGE2 level was greater in group E than group P (3.75±1.41pg/ml vs. 2.63±0.89pg/ml, respectively, p=0.011). Compared to healthy controls (1.05±0.19%), the percentage of Th17 cells was significantly greater in group P (1.52±0.62%, p=0.031), and the percentage in group E (2.99±1.09%, p<0.001) was significantly greater than in group P. The IL-17 expressions were similar. VAS pain score was positively correlated with Th17 proportion (r=0.489, p=0.003), and IL-17 concentration (r=0.458, p=0.007). PGE2 was also positively correlated with Th17 proportion (r=0.539, p=0.001), and IL-17 concentration (r=0.500, p=0.003). The expression of IL-17 was higher in the cells of group E and group P compared with normal tissue (p<0.001). CONCLUSIONS: Immune system activation is responsible, at least in part, for the pain experienced by patients with LDH, and increased levels of Th17 lymphocytes and IL-17 contribute to the pain.

Radiation-recall myositis presenting as low-back pain (2010: 4b).

We report on a patient with a history of Ewing sarcoma who underwent surgery and subsequent adjuvant chemotherapy and radiotherapy. He developed low-back pain 6 months after the end of the radiotherapy and during consolidation chemotherapy. Magnetic resonance imaging showed evidence of myositis corresponding to the 'radiation-recall phenomenon', an inflammatory reaction of irradiated tissue.

The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn's disease.

BACKGROUND: Sacroiliitis is a recognized complication of Crohn's disease and may occur distinct from progressive ankylosing spondylitis (AS). AIM: To estimate prospectively the prevalence of sacroiliitis in patients with established Crohn's disease, to characterize the clinical features and to correlate these with the presence of HLA-B27. METHODS: All Crohn's disease patients under active follow-up of between 5 and 12 years duration were invited to participate. Patients underwent a clinical evaluation including symptom questionnaire, rheumatological examination and underwent HLA genotyping. Patients then underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The clinical and radiological factors were correlated with HLA-B27 status. RESULTS: 56 patients underwent initial assessment and 44 had MRI scans. Seventeen of 44 (39%) patients had MRI evidence of sacroiliitis, of whom 5 fulfilled the criteria for AS. Symptoms of low back pain were elicited in a majority of these patients--11/17 (65%) compared to 3 of 27 (11%) patients with normal scans (P = 0.003). There were no differences in functional indices with the exception of patients with AS. HLA-B27 was present in seven patients, and all seven had MRI evidence of sacroiliitis, five had AS. CONCLUSIONS: Sacroiliitis is common in patients with established Crohn's disease and in the majority of cases, patients have symptoms of inflammatory low back pain if questioned carefully. HLA-B27 is not associated with isolated sacroiliitis, but is associated with AS. However, possession of HLA-B27 appears to convey a very high risk of developing axial inflammation in Crohn's disease.