Bone Density and Fractures in Autosomal Dominant Hyper IgE Syndrome

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• 作者：Kathryn J. Sowerwine (1)
  Pamela A. Shaw (2)
  Wenjuan Gu (3)
  Jennifer C. Ling (4)
  Michael T. Collins (5)
  Dirk N. Darnell (1)
  Victoria L. Anderson (1)
  Joie Davis (1)
  Amy Hsu (1)
  Pamela Welch (3)
  Jennifer M. Puck (6)
  Steven M. Holland (1)
  Alexandra F. Freeman (1)
  
• 关键词：Autosomal dominant hyper IgE syndrome (AD ; HIES) ; job’s syndrome ; signal transducer and activator of transcription 3 (STAT3) ; osteoporosis ; retained primary teeth
• 刊名：Journal of Clinical Immunology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：34
• 期：2
• 页码：260-264
• 全文大小：155 KB
• 参考文献：1. Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007;448(7157):1058-2. Research Support, Non-U.S. Gov’t. CrossRef
  2. Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics. 1972;49(1):59-0. In Vitro.
  3. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357(16):1608-9. Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t. CrossRef
  4. Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, et al. Hyper-IgE syndrome with recurrent infections—an autosomal dominant multisystem disorder. N Engl J Med. 1999;340(9):692-02. Research Support, Non-U.S. Gov’t. CrossRef
  5. Cohen-Solal M, Prieur AM, Prin L, Denne MA, Launay JM, Graulet AM, et al. Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome. Clin Immunol Immunopathol. 1995;76(1 Pt 1):75-1. Comparative Study In Vitro. CrossRef
  6. Zhang Z, Welte T, Troiano N, Maher SE, Fu XY, Bothwell AL. Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice. Biochem Biophys Res Commun. 2005;328(3):800-. Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. CrossRef
  
• 作者单位：Kathryn J. Sowerwine (1)
  Pamela A. Shaw (2)
  Wenjuan Gu (3)
  Jennifer C. Ling (4)
  Michael T. Collins (5)
  Dirk N. Darnell (1)
  Victoria L. Anderson (1)
  Joie Davis (1)
  Amy Hsu (1)
  Pamela Welch (3)
  Jennifer M. Puck (6)
  Steven M. Holland (1)
  Alexandra F. Freeman (1)
  
  1. Laboratories of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA
  2. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
  3. Biostatistics Research Branch, Clinical Research Directorate/CMRP SAIC-Frederick, National Laboratory for Cancer Research, Frederick, MD, 21703, USA
  4. Department of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA
  5. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, Bethesda, MD, USA
  6. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
  
• ISSN：1573-2592

文摘

Purpose Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover. Methods Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately. Results Twenty-three AD-HIES children (6-8?years) and 33 AD-HIES adults (21-0?years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61?%) had histories of minimal trauma fractures, as did 26 of the 33 adults (79?%). Osteopenia or osteoporosis was found in 79?% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures. Conclusions Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.