SAPHO Syndrome
Conditions
Brief summary
SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a chronic inflammatory rheumatism associating bone or joint lesions and dermatological manifestations dominated by severe acne and palmar and palmoplantar pustulosis. Prevalence of SAPHO syndrome is estimated at 1/50000 in France, but this figure is probably underestimated due to frequent misdiagnosis. Osteoarticular manifestations form a rheumatic picture very similar to that of other forms of spondyloarthritis (SpA). The latest French recommendations do not distinguish SAPHO syndrome from other forms of SpA. As a result, the management of SAPHO remains fairly heterogeneous, essentially based on the local experience of rheumatologists. Delays in diagnosis and difficulties in finding effective treatment can result in significant disability and reduced quality of life, particularly detrimental in a young population (age at diagnosis is usually between 30 and 40). The wide spectrum of clinical presentations of SAPHO syndrome explains the complexity of managing this condition. Understanding the pathophysiological mechanisms underlying these different forms of the disease is a major challenge for personalized medicine. SAPHO syndrome is a multifactorial disease that is a result of interaction of genetic, environmental, immunological and infectious factors. In the classification of immune-mediated inflammatory diseases, SAPHO syndrome lies midway between autoinflammatory diseases involving the innate immune response and spondyloarthritis associated with abnormalities in the adaptive immune response. Indeed, while the clinical phenotype may resemble spondyloarthritis in certain aspects, the identification of genetic forms of chronic relapsing osteitis, such as DIRA syndrome or Majeed syndrome, argues in favor of an autoinflammatory origin of SAPHO syndrome. Although osteitis is reputed to be sterile, an infectious initiating factor has long been suspected in this disease. Among the bacterial agents, antigens antigens from Cutibacterium acnes were detected in bone biopsies from patients with SAPHO syndrome. It has been suggested that this bacterium may play a role in triggering a systemic inflammatory response systemic inflammatory response mediated in particular by IL-1β.
Detailed description
Although neutrophils (PNN) are the most abundant leukocytes in the circulation and form a first line of innate immune defense, they are difficult to study because they have a short lifespan and, after migrating into tissues, are rapidly eliminated by macrophages. PNN play a central role in the early phase of SpA development, and contribute to the various tissue damage observed. PNN are recruited from the circulation and enter target tissues such as joints, enthesis, digestive tract, skin and eyes, where they produce neutrophil extracellular traps (NETs), cytokines and chemokines that attract other immune cells. In SAPHO syndrome, bone biopsy usually reveals an infiltrate of PNNs, at least in the early stages of the disease. To date, no study has performed extensive phenotyping of circulating blood to identify over- or under-represented cell populations, which could thus be implicated in the disease. Studies showed an increase in the Th17 population in SAPHO patients, elevated low density granulocytes and neutrophil extracellular traps formation, as well as specific protein patterns associated with inflammation. Genetic studies, particularly in Chinese populations, have revealed potential associations with IL-23R and IL-4 genes, as well as SNPs in PEX16 and IQCA1L. However, no large-scale genetic analysis has been conducted in European/Caucasian populations. While certain forms of SAPHO syndrome suggest a genetic predisposition, studies targeting genes associated with monogenic disorders like Majeed, PAPA, and DIRA have yielded negative results. Chinese studies have indicated involvement of genes like CSF2RA, NOD2, MEGF6, and ADAM5. Despite genetic predisposition suspicions, robust associations have not been identified, particularly in Caucasian populations, warranting further research.
Interventions
OTHERbiological sampling
DNA and Cells will be sampled
Sponsors
Fondation Hôpital Saint-Joseph
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient aged ≥ 18 years * Patient diagnosed with SAPHO syndrome * Weight \> 35 kg * Patient affiliated with a health insurance plan * French-speaking patient * Patient who has given free, informed, and written consent
Exclusion criteria
* Patient under guardianship or curatorship * Patient deprived of liberty * Patient under legal protection * Pregnant or breastfeeding patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigating a Genetic Predisposition to SAPHO Syndrome | at baseline | Comparison of allelic frequencies in patients with SAPHO syndrome versus the general population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimating the Degree of Genetic Component Overlap Between SAPHO Syndrome and Axial SpA | at baseline | Comparison of allelic frequencies in patients with SAPHO syndrome versus patients with severe and non-severe axial SpA |
| Studying the Genetic Component Based on Different Phenotypes of SAPHO Syndrome | at baseline | comparison of allelic frequencies among patients: With pure osteitis form of SAPHO syndrome vs. those with axial form of the disease With cutaneous involvement vs. without cutaneous involvement |
| Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the protein level | at baseline, at 6 months, and every year for 9 years | comparison of Expression level of protein of the different variants in sorted cells and plasma |
| Studying the Functional Consequences of Variants Associated with SAPHO Syndrom, on the transciptom level | at baseline, at 6 months, and every year for 9 years | comparison of Expression level of mRNA of the different variants in sorted cells and plasma |
| Measurement of Cytokines of Interest | at baseline and at 6months | Dosage of cytokine done by ELISA in the plasma of SAPHO patients and control populations. |
| Identification of Prognostic Factors for Severity of SAPHO Syndrome and/or Response to Different Treatments | at baseline and at 6months | clinical evalution of the severity of the disease and its response to the treatment |
| Phenotypic Characterization of Different Circulating Immune Subpopulations in Patients with SAPHO Syndrome | at baseline and at 6months | percentage of the different circulating immune cell subtypes (monocytes, T lymphocytes and subclasses, B lymphocytes, PNN, and NK) and rare populations (MAIT, γδ lymphocytes, etc.) determined by flow cytometry techniques |
Countries
France
Contacts
Primary ContactOlivier Fogel, MD
Outcome results
None listed