Immunoglobulin replacement therapy: a twenty-year review and current update.

OBJECTIVE: The expansion of immunoglobulin replacement to multiple disease entities marks a decade-long advancement in immune therapy. Parallel to its extension, the characteristics and composition of immunoglobulin products have diversified. The aim of this study was to summarize a 20-year comprehensive literature review of currently commercially available immunoglobulin products, particularly examining individual product properties in a comparative format. Data Sources/Study Selections: The literature review was performed using PubMed and Ovid, screening a time span of 2 decades. Both authors reviewed the obtained articles for acceptable quality, and the selection was narrowed down based on criteria for randomized clinical and therapeutic trials. RESULTS: Product-specific characteristics in terms of purification strategy, stabilizers, composition, and viral inactivation were found among the immunoglobulin products investigated. Such differing characteristics manifest in their variable clinical safety and efficacy as assessed by the comparative product analysis. In subgroups of patients, subcutaneous immunoglobulin therapy may be an alternative to intravenous immunoglobulin (IVIG) therapy with an equal efficacy and a lower number of systemic adverse events. CONCLUSION: Only few comprehensive clinical synopses are available to clearly demonstrate the differences in IVIG products despite the widespread clinical use of the therapy. This review defines significant characteristics of individual immunoglobulin products, noting important differences in product development and application and allowing informed clinical decisions to match a product with patients' risk factors and comorbidity. This balanced approach to gammaglobulin replacement therapy is imperative to produce the highest clinical efficacy and lowest number of adverse events.

No pathogenic mutations identified in the COL8A1 and COL8A2 genes in familial Fuchs corneal dystrophy.

PURPOSE: To investigate the genetic basis of late-onset, familial Fuchs endothelial corneal dystrophy (FECD) through screening of the COL8A1 and COL8A2 genes, in which mutations have been associated with both early and late-onset, familial and sporadic FECD. METHODS: DNA extraction, PCR amplification, and direct sequencing of the COL8A1 and COL8A2 genes was performed in affected and unaffected members of 15 unrelated families with two or more members with late-onset FECD. RESULTS: Screening of the COL8A1 gene did not reveal sequence variants in any affected individuals from the 15 FECD families. In the COL8A2 gene, the previously identified mutations presumed to play a pathogenic role in cases of familial FECD (Arg155Gln, Leu450Trp, and Gln455Lys) were not discovered in any of the affected patients. A mutation previously considered causative of FECD (Arg434His) was shown not to segregate with the disease in the one family in which it was identified. Two previously identified single-nucleotide polymorphisms (SNPs), Pro575Leu and Pro586Pro, were identified in a single affected individual and three affected individuals (two families), respectively. CONCLUSIONS: The Arg434His mutation in the COL8A2 gene, previously associated with FECD, has been shown not to segregate with the disease phenotype, and thus may not be considered a disease-causing mutation. The absence of pathogenic mutations identified in the COL8A1 or COL8A2 genes in affected members of 15 pedigrees with familial FECD indicates that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.