Background: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype... Show moreBackground: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms. Objectives: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of terms, and to reannotate IEIs with HPO terms to provide accurate, standardized phenotypic descriptions. Methods: We initiated a collaboration involving expert clinicians, geneticists, researchers working on IEIs, and bioinformaticians. Multiple branches of the HPO tree were restructured and extended on the basis of expert review. Our ontology-guided machine learning coupled with a 2-tier expert review was applied to reannotate defined subgroups of IEIs. Results: We revised and expanded 4 main branches of the HPO tree. Here, we reannotated 73 diseases from 4 International Union of Immunological Societies-defined IEI disease subgroups with HPO terms. We achieved a 4.7-fold increase in the number of phenotypic terms per disease. Given the new HPO annotations, we demonstrated improved ability to computationally match selected IEI cases to their known diagnosis, and improved phenotype-driven disease classification. Conclusions: Our targeted expansion and reannotation presents enhanced precision of disease annotation, will enable superior HPO-based IEI characterization, and hence benefit both IEI diagnostic and research activities. Show less
Borsato, L.; Piotto, G.; Gandolfi, D.; Nascimbeni, V.; Lacedelli, G.; Marzari, F.; ... ; Walton, N. van 2021
Background Patients with an IgG subclass deficiency (IgSD) +/- specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown... Show moreBackground Patients with an IgG subclass deficiency (IgSD) +/- specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. Objective To compare the efficacy of PA and IRT in a randomized crossover trial. Methods A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. Results The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). Conclusion We found comparable efficacy of IRT and PA in patients with IgSD +/- SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. Clinical Implication Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA. Show less
Szegedi-Elek, E.; Ábrahám, P.; Wyrzykowski, Ł.; Kun, M.; Kóspál, Á.; Chen, L.; ... ; Ziółkowska, O. 2020
Objective. Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of... Show moreObjective. Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of LSTVs and to assess their associations with sacroiliitis by standard radiography and MRI in a population with suspected axial spondyloarthritis.Methods. The data were from the DESIR cohort of 688 patients aged 18-50 years with inflammatory low back pain for 3 months but <3 years suggesting axial spondyloarthritis. The baseline pelvic radiographs were read by two blinded readers for the presence and type (Castellvi classification) of LSTVs. Associations between LSTVs and other variables collected at baseline and at the diagnosis were assessed using the chi(2) test (or Fisher's exact test) or the Mann-Whitney test.Results. LSTV was found in 200/688 (29.1%) patients. Castellvi type was Ia in 54 (7.8%), Ib in 76 (11.0%), IIa in 20 (2.9%), IIb in 12 (1.7%), IIIa in 7 (1.0%), IIIb in 21 (3.0%) and IV in 10 (1.4%) patients. Compared with the group without LSTVs, the group with LSTVs had higher proportions of patients meeting modified New York criteria for radiographic sacroiliitis (19% vs 27%, respectively; P = 0.013) and Assessment of SpondyloArthritis international Society MRI criteria for sacroiliitis (29% vs 39%, respectively; P = 0.019).Conclusion. In patients with inflammatory back pain suggesting axial spondyloarthritis, LSTVs are associated with both radiographic and MRI sacroiliitis. Show less
Voirin-Hertz, M.; Alegria, G.C.; Garrigues, F.; Simon, A.; Feydy, A.; Reijnierse, M.; ... ; Saraux, A. 2020
Objective: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and... Show moreObjective: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and imaging-study in patients with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA).Methods: Baseline weight-bearing lumbar-spine radiographs obtained in the DESIR cohort of patients aged 18-50 years and having IBP for at least 3 months but less than 3 years suggesting axSpA were studied. After training on scoliosis detection based on Cobb's angle>10 degrees plus Nash-Moe grade >= 1, readers blinded to patient data measured spine lumbar scoliosis, sacral horizontal angle, lumbosacral angle and lumbar lordosis on the radiograph of the lumbar and scored sacroiliitis on the radiograph of the pelvis. Baseline MRIs T1 and STIR of the lumbar spine and sacroiliac joints were evaluated for respectively degenerative changes and signs of axSpA.Results: Of the 360 patients (50.8% females) 88.7% had lumbar pain and 69.3% met ASAS criteria for axSpA. Mean Cobb's angle was 3.2 degrees +/- 5.0 degrees and 28 (7.7%) patients had lumbar scoliosis. No statistical differences were observed for radiographic sacroiliitis, MRI sacroiliitis, modified Stoke Ankylosing Spondylitis Spinal Score, Pfirmmann score, high-intensity zone, protrusion, extrusion, MODIC score between patients with and without scoliosis. In both groups, degenerative changes by MRI were rare and predominated at L4-L5 and L5-S1.Conclusion: In patients with early IBP suggesting axSpA, lumbar scoliosis was not associated with inflammatory or degenerative changes. (C) 2019 Elsevier Inc. All rights reserved. Show less
Alegria, G.C.; Deloire, L.; Herbette, M.; Garrigues, F.; Gossec, L.; Simon, A.; ... ; Saraux, A. 2020
Objective. To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain.Methods.... Show moreObjective. To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain.Methods. Spinal-pelvic orientation was assessed in DESIR cohort patients with recent-onset inflammatory back pain and suspected axSpA, by using lateral lumbar-spine radiographs to categorize sacral horizontal angle (<40 degrees vs >= 40 degrees), lumbosacral angle (<15 degrees vs >= 15 degrees) and lumbar lordosis (LL, <50 degrees vs >= 50 degrees). Associations between these angle groups and variables collected at baseline and 2 years later were assessed using the chi(2) test (or Fisher's exact) and the Mann-Whitney test. With Bonferroni's correction, P < 0.001 indicated significant differences.Results. Of 362 patients, 358, 356 and 357 had available sacral horizontal angle, lumbosacral angle and LL values, respectively; means were 39.3 degrees, 14.6 degrees and 53.0 degrees, respectively. The prevalence of sacroiliitis on both radiographs and MRI was higher in the LL < 50 degrees group than in the LL >= 50 degrees group, but the difference was not statistically significant. Clinical presentation and confidence in a diagnosis of axSpA did not differ across angle groups. No significant differences were identified for degenerative changes according to sacral horizontal angle, lumbosacral angle or LL.Conclusion. Spinal-pelvic balance was not statistically associated with the clinical or imaging-study findings suggesting axSpA in patients with recent-onset inflammatory back pain. Show less
Lubbers, R.; Beaart-van De Voorde, L.J.J.; Leeuwen, K. van; Boer, M. de; Gelderman, K.A.; Berg, M.J. van den; ... ; Trouw, L.A. 2019
