Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency

Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10−57; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10−17; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10−35; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH)

Immunoglobulin A deficiency and oral health status: a case-control study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldINTRODUCTION: Immunoglobulin A (IgA) is important for mucosal health. Selective IgA deficiency (IgAD) is the most common primary immunodeficiency but its effect on oral health is unclear. The aim of this study was to investigate dental, periodontal and oral mucosal health in IgAD individuals. MATERIAL AND METHODS: In total, 32 adult IgAD subjects were compared with 63 randomly selected individuals. Participants answered questionnaires regarding general and oral health and underwent oral examination, including examination using the periodontal screening and recording (PSR) system and dental examination using the DMF system. RESULTS: The IgAD individuals had significantly more often undergone tonsillectomy (44%versus 24%, p=0.046) and adenoidectomy (31%versus 8%, p=0.003) compared with the controls. Furthermore, the IgAD subjects reported having pharyngitis, stomatitis and herpes labialis significantly more often. There was no significant difference in periodontal health (mean PSR index; 1.87 versus 1.77) or dental health (mean DMFS; 51.3 versus 53.7) between the two cohorts. A positive correlation between Helicobacter pylori infection and severity of periodontitis was found (p=0.036). CONCLUSION: IgAD predisposes to oral mucosal infections but does not influence periodontal or dental health. This is the first controlled study to include detailed clinical history and investigations, together with full oral and dental examination, in adults with IgAD

Gloria McLarty and her spinning group, Hamilton, Victoria, ca. 1975 [picture] /

Gloria, third from right, was a spinner and weaver and a pioneer of the craft movement in Western Victoria in the seventies.; Part of: Sheilas, a tribute to Australian women collection, ca. 1975.; Title devised by cataloguer based on information supplied by photographer.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4227608

Alpaca embryo transfer at Canchones, Dr. Jane Vaughan uses an ultrasound scan to check recipient female Alpaca for gynaecological suitability before transferring an embryo, Taggerty, Victoria, 2007 [picture] /

Title devised by cataloguer based on caption list supplied by photographer.; Acquired in digital format; access copy available online.; Mode of access: Internet via World Wide Web.; Purchased frm the photographer, June Orford, 2007

Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTo understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1,090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10(-10)) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10(-7)), and 29 additional loci were identified with P < 5 x 10(-5). A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10(-4)) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD

Representation of the haplotypes carrying the <i>HLA-DRB1</i> alleles most associated with IgAD.

<p>Reconstructed extended haplotypes using the final set of 49 SNPs spanning the classical HLA region were aligned to the respective extended haplotype. Shown here are the reconstructed haplotypes carrying the HLA-DRB1*03 (a), -DRB1*07 (b), -DRB1*0102 (c) and -DRB1*15 (d) alleles. Recombinant haplotypes represent all haplotypes containing the same <i>HLA-DRB1</i> allele in association with a different <i>HLA-B</i> allele, as compared to the respective extended haplotype. Vertical bars delimit the HLA Class III region. N, Number of haplotypes. Haplotype frequencies in the Swedish/Icelandic, Spanish and Icelandic cohorts are detailed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002476#pgen-1002476-t001" target="_blank">Table 1</a>.</p