Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.
Arthritis Rheum
; 48(9): 2632-44, 2003 Sep.
Article
en En
| MEDLINE
| ID: mdl-13130484
ABSTRACT
OBJECTIVE:
To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS.METHODS:
Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes.RESULTS:
Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants.CONCLUSION:
The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fiebre Mediterránea Familiar
/
Periodicidad
/
Antígenos CD
/
Receptores del Factor de Necrosis Tumoral
/
Heterogeneidad Genética
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Arthritis Rheum
Año:
2003
Tipo del documento:
Article
País de afiliación:
Reino Unido