| Full text | |
| Author(s): Show less - |
Jesus, Adriana A.
[1]
;
Osman, Mazen
[2]
;
Silva, Clovis A.
[1]
;
Kim, Peter W.
[3]
;
Pham, Tuyet-Hang
[4]
;
Gadina, Massimo
[4]
;
Yang, Barbara
[4]
;
Bertola, Debora R.
[1]
;
Carneiro-Sampaio, Magda
[1]
;
Ferguson, Polly J.
[5]
;
Renshaw, Blair R.
[6]
;
Schooley, Ken
[6]
;
Brown, Michael
[6]
;
Al-Dosari, Asma
[2]
;
Al-Alami, Jamil
[2]
;
Sims, John E.
[6]
;
Goldbach-Mansky, Raphaela
[4]
;
El-Shanti, Hatem
[2, 5]
Total Authors: 18
|
| Affiliation: | [1] Univ Sao Paulo, Sao Paulo - Brazil
[2] Shafallah Med Genet Ctr, Doha - Qatar
[3] NIAMSD, NIH, Bethesda, MD 20892 - USA
[4] Tuyet-Hang Pham, NIAMSD, NIH, Bethesda, MD 20892 - USA
[5] Univ Iowa, Carver Coll Med, Iowa City, IA - USA
[6] Amgen Inc, Seattle, WA - USA
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | ARTHRITIS AND RHEUMATISM; v. 63, n. 12, p. 4007-4017, DEC 2011. |
| Web of Science Citations: | 42 |
| Abstract | |
Objective Monogenic autoinflammatory diseases are disorders of Mendelian inheritance that are characterized by mutations in genes that regulate innate immunity and whose typical features are systemic inflammation without high-titer autoantibodies or antigen-specific T cells. Skin and bone inflammation in the newborn period have been described in 3 of these autoinflammatory disorders: neonatal-onset multisystem inflammatory disease, Majeed syndrome, and deficiency of interleukin-1 (IL-1) receptor antagonist (DIRA) syndrome. This study was undertaken to present the characteristics of the DIRA syndrome in 2 cases from Brazil, and describe a novel mutation in IL1RN. Methods. Two unrelated Brazilian patients were evaluated for the clinical signs and symptoms of these 3 disorders, and peripheral blood samples were assessed for mutations in NLRP3, LPIN2, and IL1RN by DNA resequencing analysis. A mutation in IL1RN that encodes a mutant protein was identified, and the expression and function of this mutant protein were compared to those of the wild-type protein. Results. Both patients presented with pustular dermatitis resembling generalized pustular psoriasis, recurrent multifocal aseptic osteomyelitis, and elevation in the levels of acute-phase reactants, all of which are features most consistent with the DIRA syndrome. Chronic lung disease was observed in 1 of the patients, and jugular venous thrombosis was observed in the other patient. Both patients showed a partial response to corticosteroid therapy, and 1 patient experienced an initial improvement of dermatitis with the use of acitretin. Both patients were homozygous for a novel 15-bp (in-frame) deletion on the IL1RN gene. The mutated protein expressed in vitro had no affinity with the IL-1 receptor, and stimulation of the patients' cells with recombinant human IL-1 alpha or IL-1 alpha led to oversecretion of proinflammatory cytokines, similar to the findings obtained in previously reported patients. Conclusion. The presence of the same homozygous novel mutation in IL1RN in 2 unrelated Brazilian patients suggests that this genetic variant may be a founder mutation that has been introduced in the Brazilian population. (AU) | |
| FAPESP's process: | 02/05880-4 - Primary immunodeficiences in high risk pediatric patients: relationships between clinical manifestations and genetic alterations |
| Grantee: | Magda Maria Sales Carneiro-Sampaio |
| Support Opportunities: | Research Projects - Thematic Grants |