HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.

The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease.

Reciprocal interactions between host T helper cells and gut microbiota enforce local immunological tolerance and modulate extra-intestinal immunity. However, our understanding of antigen-specific tolerance to the microbiome is limited. Here, we developed a systematic approach to predict HLA class-II-specific epitopes using the humanized bacteria-originated T cell antigen (hBOTA) algorithm. We identified a diverse set of microbiome epitopes spanning all major taxa that are compatible with presentation by multiple HLA-II alleles. In particular, we uncovered an immunodominant epitope from the TonB-dependent receptor SusC that was universally recognized and ubiquitous among Bacteroidales. In healthy human subjects, SusC-reactive T cell responses were characterized by IL-10-dominant cytokine profiles, whereas in patients with active Crohn's disease, responses were associated with elevated IL-17A. Our results highlight the potential of targeted antigen discovery within the microbiome to reveal principles of tolerance and functional transitions during inflammation.

Do Infant Cleft Dimensions Have an Influence on Occlusal Relations? A Subgroup Analysis Within an RCT of Primary Surgery in Patients With Unilateral Cleft Lip and Palate.

AIM: To investigate whether infant cleft dimensions, in a surgical protocol with early or delayed hard palate closure, influence occlusion before orthodontics. DESIGN: Subgroup analysis within a randomized trial of primary surgery (Scandcleft). SETTING: Tertiary health care. One surgical centre. PATIENTS AND METHODS: A total of 122 unilateral cleft lip and palate infants received primary cheilo-rhinoplasty and soft palate closure at age 4 months and were randomized for hard palate closure at age 12 versus 36 months. A novel 3D analysis of cleft size and morphology was performed on digitized presurgical models. Occlusion was scored on 8-year models using the modified Huddarth-Bodenham (MHB) Index and the Goslon Yardstick. MAIN OUTCOME MEASUREMENTS: Differences in MHB and Goslon scores among the 2 surgical groups adjusted for cleft size. RESULTS: The crude analysis showed no difference between the 2 surgical groups in Goslon scores but a better MHB (P = .006) for the group who received delayed hard palate closure. When adjusting for the ratio between cleft surface and palatal surface (3D Infant Cleft Severity Ratio) and for posterior cleft dimensions at tuberosity level, the delayed hard palate closure group received 3.65 points better for MHB (confidence interval: 1.81; 5.48; P < .001) and showed a trend for reduced risk of receiving a Goslon of 4 or 5 (P = .052). For posterior clefts larger than 9 mm, the Goslon score was better in the delayed hard palate closure group (P = .033). CONCLUSIONS: Seen from an orthodontic perspective, when the soft palate is closed first, and the cleft is large, the timing of hard palate closure should be planned in relation to posterior cleft size.

Condylar changes in patients with idiopathic condylar resorption: retrospective 2-year follow-up CBCT-based case-control study.

OBJECTIVES: To compare condylar development and changes in condylar radiological appearance in patients with idiopathic condylar resorption (ICR) to a healthy, age- and gender matched, control group. MATERIALS AND METHODS: This case-control study included 16 ICR patients [mean age: 15years, 9 months; standard deviation (SD): 4 years) and 16 controls (mean age: 16 years, 8 months; SD: 4 years, 7 months), with diagnostic (T0) and 2-year follow-up (T1) CBCT examinations. Condylar changes were evaluated through changes in condylar neck angle (CNA), and the transversal, vertical and anteroposterior displacement of five condylar points between T0 and T1. The magnitude and direction of condylar changes were evaluated using vector analyses. A qualitative radiological evaluation of the TMJ was performed based on healthy, erosive and repaired morphological appearance. Linear and angular measurements were assessed using ANOVA and a Tukey post-hoc test, and vectors were tested using an independent-sample 2-tailed t-test. Fisher's exact test was used for the qualitative evaluation. RESULTS: At T0, ICR patients exhibited decreased condylar height, smaller condylar width and posteriorly inclined CNA compared with the control group (P < 0.05). During observation, condylar vertical growth was smaller in the ICR group than in the control group (P < 0.05). Vector analysis showed an upward direction of vertical displacement for all condylar points in the control group; the ICR group showed a downward direction (P < 0.003). The radiological appearance of 75% of the ICR condyles and 94% of the control condyles did not change during the 2-year follow-up period. CONCLUSIONS: ICR condyles displayed reduced vertical development compared with control condyles. The radiological appearance remained unchanged for most joints. Observed changes in radiological appearance did not always follow a progressive model of degenerative joint disease.

Time to Reconsider Management of the Temporomandibular Joint in Juvenile Idiopathic Arthritis.

The temporomandibular joints are often affected by juvenile idiopathic arthritis, but few evidence-based management strategies exist. Intra-articular steroid injection (IASI) is a common intervention and is associated with pain reduction and improved mandibular function. Emerging evidence, however, suggests that IASI may actually impair rather than improve mandibular growth. It is therefore time to reconsider this practice.

Orthopaedic splint treatment can reduce mandibular asymmetry caused by unilateral temporomandibular involvement in juvenile idiopathic arthritis.

Unilateral temporomandibular joint (TMJ) arthritis in juvenile idiopathic arthritis (JIA) patients often induces asymmetric dentofacial growth. This study evaluates the effects of an orthopaedic functional appliance worn full time to reduce asymmetric mandibular growth in JIA patients. Twenty-two JIA patients with unilateral TMJ involvement were included in the study (mean age 7.5 years, range: 3.8-13.8 years). They all received orthopaedic treatment with a functional appliance, a so-called distraction splint (mean treatment time 57 months). Panoramic tomograms or cone beam-computerized tomograms were taken before and within 12 months after treatment cessation. At both time points, the ratio between the healthy and the affected side of the mandible was evaluated in terms of inter-side differences in condylar height, ramus height, and total vertical mandibular height. Orthopaedic functional treatment reduced mandibular asymmetries in terms of ramus height and total vertical mandibular height (P < 0.05). Mandibular growth rates in the affected and the non-affected sides were comparable in most patients. Our study finds evidence to support that a distraction splint can normalize mandibular vertical growth in the affected side. We therefore suggest implementation of distraction splint therapy in the treatment of JIA patients with unilateral TMJ arthritis.

Assessment of Orofacial Symptoms in Juvenile Idiopathic Arthritis: Validation of a Consensus-Based Short Patient Questionnaire.

OBJECTIVE: To develop, validate, and test the performance of patient-reported outcomes (PROs) in a short patient questionnaire (< 5 minutes in length) in order to assess the multidimensional aspects of orofacial symptoms related to juvenile idiopathic arthritis (JIA) among patients aged ≥ 10 years. METHODS: The study was conducted by an interdisciplinary task force from the Temporomandibular Joint Juvenile Arthritis Working Group. The project consisted of a multiphased approach including the following: (1) conceptual phase with online international survey of 167 healthcare workers, (2) item generation and drafting of preliminary questionnaire(s) (ie, face validity), (3) cognitive script interview and probing (ie, content validity; 16 patients with JIA), (4) assessment of construct validity (ie, convergence and divergence; 53 patients with JIA), (5) test of reliability, and (6) test of clinical performance and psychometric characteristics (95 patients with JIA). RESULTS: In total, 7 PROs were included in the final patient questionnaire: (1) pain frequency, (2) pain intensity, (3) pain location, (4) jaw function, (5) specific questions related to symptoms and dysfunction, (6) changes in face and jaw pain since last visit, and (7) changes in jaw function since last visit. In total, 80% of the patients were able to complete the questionnaire in less than 5 minutes. CONCLUSION: We have developed and validated a short patient questionnaire to assess the multidimensional aspects of JIA-related orofacial symptoms. The PROs included in our questionnaire show acceptable validity and reliability. The questionnaire is applicable to routine monitoring of subjects with JIA, as well as future research studies.

Incidence of Orofacial Manifestations of Juvenile Idiopathic Arthritis From Diagnosis to Adult Care Transition: A Population-Based Cohort Study.

OBJECTIVE: To estimate the cumulative incidences of orofacial conditions related to temporomandibular joint (TMJ) juvenile idiopathic arthritis (JIA) between diagnosis in childhood to transition into adult care, and to identify features in JIA associated with TMJ involvement. METHODS: A population-based cohort analysis was conducted of patients with JIA involving longitudinal data on orofacial health from 2000 to 2018. Regardless of TMJ status, the patients were referred to the Regional Specialist Craniofacial Clinic of Western Denmark for routine orofacial examinations. Data collection included information about disease-specific background characteristics, TMJ involvement, JIA-induced dentofacial deformity, and orofacial symptoms and dysfunction. RESULTS: A total of 613 patients were followed up with a mean clinical TMJ observation time of 4.0 years. From JIA onset to transition into adult care, the cumulative incidence of patients with JIA involvement of the TMJ was 30.1%. Furthermore, 20.6% of the cohort had developed arthritis-induced dentofacial deformity. A substantial proportion of the cohort experienced several events with orofacial symptoms (23.5%) and dentofacial dysfunction (52%). Young age at diagnosis (<9 years), female gender, and antinuclear antibody positivity were significantly associated with TMJ involvement. CONCLUSION: Orofacial signs and symptoms were frequent findings in children and adolescents with JIA. TMJ involvement was seen in 30.1% of the cohort; and 20.6% of the total cohort developed JIA-related dentofacial deformity before transition into adult care. This is the first population-based study in the era of available biologic treatments to document these frequent orofacial complications in children with JIA.

Management of Orofacial Manifestations of Juvenile Idiopathic Arthritis: Interdisciplinary Consensus-Based Recommendations.

Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA.

Association between condylar morphology and changes in bony microstructure and sub-synovial inflammation in experimental temporomandibular joint arthritis.

BACKGROUND: In juvenile idiopathic arthritis involvement of the temporomandibular joints (TMJs) is often associated with mandibular growth deviations. The relation between the growth deviations and severity of the inflammation, condylar shape, the micro-architecture, and the quality of the bone has not previously been investigated. This paper studies the effect on the bony structures in mandibular condylar development in rabbits with antigen-induced arthritis. METHODS: Included were 42 juvenile rabbits with ovalbumin-induced arthritis of the TMJs treated with intraarticular saline, intraarticular etanercept or subcutaneous etanercept. A TMJ from each animal was scanned using micro-computed tomography and structural parameters were calculated. Three-dimensional reconstructions of the mandibular condyle were scored blindly as normal or abnormal. TMJs were stratified for condylar morphology and were evaluated against data on trabecular structural parameters, inflammation, degree of mineralization, overall mandibular growth, and mineral apposition rate. RESULTS: Abnormal morphology were seen in 15/32 animals available for data analysis. Erosions were an uncommon finding. Abnormal morphology was strongly related to the degree of inflammation. The trabecular separation was larger in group with abnormal morphology than in the group with normal morphology. Abnormal condylar morphology was not associated with overall mandibular growth. No differences were observed in mineral apposition rate. No differences in structural parameters were seen according to treatment modality. CONCLUSION: We showed that severe inflammation in the TMJs during mandibular development was associated with morphological changes in the mandibular condyle. These changes were predominantly seen at the macro-morphological level and only very few differences were structural.

Cumulative Incidence of Orofacial Manifestations in Early Juvenile Idiopathic Arthritis: A Regional, Three-Year Cohort Study.

OBJECTIVE: To estimate the cumulative incidence of arthritis-induced orofacial symptoms, dysfunction, and dentofacial deformities in growing individuals with juvenile idiopathic arthritis (JIA) in a 36-month regional cohort study and to identify predictors for the development of arthritis-induced dentofacial deformities. METHODS: Data were retrieved from the Aarhus JIA temporomandibular joint (TMJ) cohort register, which contains standardized, longitudinal, observational data regarding orofacial conditions in patients with JIA (n = 1,040). This regional cohort represents the majority of all subjects with JIA from the western part of Denmark between 1990 and 2016, regardless of TMJ arthritis status. Cumulative incidences of orofacial conditions were reported using Kaplan-Meier methods, and predictors for dentofacial deformity were identified using Cox proportional hazards analysis. RESULTS: Follow-up data from 351 subjects for 36 months were included in this study. Median age at first clinical examination was 6.6 years (interquartile range 4.8-9.9 years). Orofacial symptoms and dysfunctions were common findings at 36 months after the first clinical examination and 5 years after JIA onset, with a cumulative incidence of 38% and 53%, respectively. Dentofacial deformities were found in 35% of subjects at the 36-month follow-up and were significantly associated with the presence of orofacial dysfunction. CONCLUSION: Orofacial conditions were frequently observed in individuals with JIA and were represented in all JIA subcategories in this regional study. One-third of subjects had arthritis-induced dentofacial deformities that required orthopedic appliance treatment at the 36-month follow-up.

Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage.

OBJECTIVE: The present study assessed somatosensory changes related to trigeminal nerve damage using extensive evaluation tools and assessed the effect of such damage on the patients' psychosocial status and quality of life compared with healthy participants. METHODS: In 37 patients with intraorally or extraorally presenting trigeminal nerve damage diagnosed as painful or nonpainful posttraumatic trigeminal neuropathy, psychophysical tests like quantitative sensory testing (QST) and qualitative sensory testing and the electrophysiological "nociceptive-specific" blink reflex were performed. The patients and 20 healthy participants completed a set of questionnaires assessing their psychosocial status and quality of life. RESULTS: A loss or gain of somatosensory function was seen in at least 1 QST parameter in >88.9% of the patients. Patients in whom extraoral QST was performed showed an overall loss of somatosensory function, whereas intraoral QST showed a general gain of somatosensory function. Qualitative sensory testing identified a side-to-side difference in the tactile and pinprick stimulation in >77% of the patients. An abnormal "nociceptive-specific" blink reflex response was seen in 42.1% to 71.4% of patients dependent on the trigeminal branch stimulated, though comparisons with healthy reference values showed ambiguous results. Compared with the healthy participants, patients showed higher scores for pain catastrophizing, symptoms of depression and anxiety, limited jaw function, more somatic symptoms, and significantly impaired oral health-related quality of life (all P<0.038). DISCUSSION: The results from the present study showed presence of varied somatosensory abnormalities when assessed using psychophysical and electrophysiological investigations and a significantly impaired psychosocial status.

Intra-articular steroid injection for temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic review on efficacy and safety.

OBJECTIVE: To determine the current level of evidence for the use of intra-articular corticosteroid injections (IACI) against temporomandibular joint (TMJ) arthritis in patients with juvenile idiopathic arthritis (JIA) with a particular focus on clinical and radiological improvements and safety profile. METHODS: A comprehensive electronic search strategy was performed in all major medical databases in February 2012. Studies were selected independently by two reviewers in accordance with a pre-specified protocol and a risk of bias assessment for all included studies. RESULTS: Ninety-four unique citations were identified of which seven remained after the inclusion criteria were applied and all of these were assessed to have a high risk of bias. The current limited level of evidence suggests potential beneficial properties of IACI in patients with TMJ arthritis-related symptoms and/or MRI-verified signs of TMJ inflammation. Currently, no scientific evidence substantiates the effect of IACI in terms of (I) improving maximal mouth opening capacity significantly, (II) reducing radiological disease progression, (III) normalising/improving mandibular growth, and (IV) increasing efficacy upon repeated injections. CONCLUSION: The current level of evidence allows only very limited conclusions on the effect of IACI therapy in patients with TMJ arthritis. Knowledge on the long-term impact of IACI on mandibular growth is not available. Future studies designed in accordance with evidence-based standards are needed to allow a more general conclusion on efficacy and safety of this treatment modality in patients with TMJ arthritis.

Orofacial symptoms related to temporomandibular joint arthritis in juvenile idiopathic arthritis: smallest detectable difference in self-reported pain intensity.

OBJECTIVE: Temporomandibular joint (TMJ) inflammation in patients with juvenile idiopathic arthritis (JIA) may lead to mandibular growth disturbances and interfere with optimal joint and muscle function. Orofacial symptoms are common clinical findings in relation to TMJ arthritis in adolescence. Knowledge about their clinical manifestation is important for TMJ arthritis diagnosis, treatment choice, and outcome evaluation. The aim of our prospective observational study was to evaluate and describe the frequency, the main complaints, and the localization of TMJ arthritis-related orofacial symptoms. The smallest detectable differences (SDD) for minimal, average, and maximal pain were estimated. METHODS: Thirty-three patients with JIA and arthritis-related orofacial symptoms in relation to 55 affected TMJ were included in our questionnaire study (mean age 14.11 yrs). Calculation of the SDD was based on a duplicate assessment 45 min after the first questionnaire was completed. RESULTS: The majority of the patients had common orofacial symptoms during mastication and maximal mouth opening procedures. Persistent orofacial symptoms were rare. The TMJ area in combination with the masseter muscle region was the orofacial region where symptoms were most common. The SDD for minimal, average, and maximal pain were between 10 and 14 mm on a visual analog scale. CONCLUSION: Our study offers new knowledge about TMJ arthritis-related orofacial symptoms that may aid diagnosis and clinical decision-making. We suggest that TMJ arthritis-related orofacial symptoms could be understood as products of the primary TMJ inflammation in combination with secondary myogenic and functional issues.

Prediction of the articular eminence shape in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis-A simulation study.

The aim of this work was to predict the shape of the articular eminence in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis (DO). Using a patient-specific musculoskeletal model of the mandible the hypothesis that the observed differences in this patient in the left and right articular eminence inclinations were consistent with minimisation of joint loads was tested. Moreover, a prediction was made of the final shape of the articular eminence after DO when the expected remodelling has reached a steady state. The individual muscle forces and the average TMJ loading were computed for each combination of articular eminence angles both before and after DO. This exhaustive parameter study provides a full overview of average TMJ loading depending on the angles of the articular eminences. Before DO the parameter study resulted in different articular eminence inclinations between left and right sides consistent with patient data obtained from CT scans, indicating that in this patient the articular eminence shapes result from minimisation of joint loads. The simulation model predicts development of almost equal articular eminence shapes after DO. The same tendency was observed in cone beam CT scans (NewTom) of the patient taken 6.5 years after surgery.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects.

BACKGROUND: Temporomandibular joint (TMJ) arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA) corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-alpha has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented. METHODS: Forty-two rabbits (10 weeks old) pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14), an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14) and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14). Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator) were used to assess and estimate the inflammation in the joints. RESULTS: The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and subsynovial inflammation also showed reduced inflammation in the systemic etanercept group. However, the thickness of the synovial lining and volume of the subsynovial connective tissue showed no differences between the groups. CONCLUSION: An anti-inflammatory effect of systemic etanercept on the synovial tissues in the temporomandibular joint was shown. However, IA etanercept at the given dose had no significant effect on the severity of chronic inflammation on the parameters here tested in ovalbumin antigen-induced arthritis.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular joint. Part II: mandibular growth.

BACKGROUND: Temporomandibular joint (TMJ) arthritis in children causes alterations in the craniomandibular growth. Resultant abnormalities include; condylar erosions, a posterior mandibular rotation pattern, micrognathia, malocclusion with an anterior open bite, altered joint and muscular function occasionally associated with pain. These alterations may be prevented by early aggressive anti-inflammatory intervention. Previously, we have shown that intra-articular (IA) corticosteroid reduces TMJ inflammation but causes additional mandibular growth inhibition in young rabbits. Local blockage of TNF-alpha may be an alternative treatment approach against TMJ involvement in juvenile idiopathic arthritis (JIA). We evaluated the anti-inflammatory effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in young rabbits in terms of mandibular growth. This article (Part II) presents the data and discussion on the effects on facial growth. In Part I the anti-inflammatory effects of systemic and IA etanercept administration are discussed. METHODS: Arthritis was induced and maintained in the TMJs of 10-week old pre-sensitized rabbits (n = 42) by four repeated IA TMJ injections with ovalbumin, over a 12-week period. One group was treated weekly with systemic etanercept (0.8 mg/kg) (n = 14), another group (n = 14) received IA etanercept (0.1 mg/kg) bilaterally one week after induction of arthritis and one group (n = 14) served as an untreated arthritis group receiving IA TMJ saline injections. Head computerized tomographic scans were done before arthritis was induced and at the end of the study. Three small tantalum implants were inserted into the mandible, serving as stable landmarks for the super-impositions. Nineteen variables were evaluated in a mandibular growth analysis for inter-group differences. All data was evaluated blindedly. ANOVA and T-tests were applied for statistical evaluation using p < 0.05 as significance level. RESULTS: Significant larger mandibular growth disturbances were observed in the group receiving IA saline injections compared with the systemic etanercept group. The most pronounced unfavourable posterior mandibular rotation pattern was observed in the group receiving IA saline injections. CONCLUSION: Intervention with systemic etanercept monotherapy equivalent to the recommended human dose allows a mandibular growth towards an original morphology in experimental TMJ arthritis. Systemic administrations of etanercept are superior to IA TMJ administration of etanercept in maintaining mandibular vertical growth.

Reduced mandibular growth in experimental arthritis in the temporomandibular joint treated with intra-articular corticosteroid.

The aim of this investigation was to study the effect of intra-articular (i.a.) corticosteroid injections (IACIs) in the temporomandibular joint (TMJ) on mandibular development in antigen-induced TMJ arthritis. Ten-week-old female New Zealand white rabbits (n = 42) were randomly divided into four groups: group A, control (no injections); group B, placebo (repeated i.a. TMJ saline injections); group C, untreated arthritis (repeated induction of TMJ arthritis); and group D, steroid (repeated induction of TMJ arthritis + IACI). All animals had two tantalum implants inserted in the right side of the mandible serving as stable landmarks for later growth analysis. One implant was inserted close to the symphysis and one in the molar region. Computerized tomographic (CT) full-head scans were carried out at 14 (T1) and 26 (T2) weeks of age. (Dropout of animals at T2; group C, n = 7, and group D, n = 3.) Absolute and relative intra- and inter-group growth variations were evaluated during the growth period by comparison of CT scans. One-way analysis of variance was used for T1 statistical analysis, and absolute intra-group and relative inter-group growth differences between T1 and T2 were evaluated by Student's t-tests. At T2, the animals in the group A had greater sagittal and vertical mandibular growth compared with the other three groups. TMJ arthritis caused diminished mandibular growth. However, relative mandibular growth was significantly less in group D. The findings of this study do not indicate a positive long-term effect in the use of IACI in the TMJ as an early treatment intervention against TMJ inflammation in growing individuals.