Mahmood Al Kindi

Secreted autoantibody repertoires in Sjögren's syndrome and systemic lupus erythematosus: A proteomic approach.

The structures of epitopes bound by autoantibodies against RNA-protein complexes have been well-defined over several decades, but little is known of the clonality, immunoglobulin (Ig) variable (V) gene usage and mutational status of the autoantibodies themselves at the level of the secreted (serum) proteome. A novel proteomic workflow is presented based on affinity purification of specific Igs from serum, high-resolution two-dimensional gel electrophoresis, and de novo and database-driven sequencing of V-region proteins by mass spectrometry. Analysis of anti-Ro52/Ro60/La proteomes in primary Sjögrens syndrome (SS) and anti-Sm and anti-ribosomal P proteomes in systemic lupus erythematosus (SLE) has revealed that these antibody responses are dominated by restricted sets of public (shared) clonotypes, consistent with common pathways of production across unrelated individuals. The discovery of shared sets of specific V-region peptides can be exploited for diagnostic biomarkers in targeted mass spectrometry platforms and for tracking and removal of pathogenic clones.

IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjögren's syndrome reveals molecular markers of Ro/La diversification.

We have used high-resolution mass spectrometry to sequence precipitating anti-Ro60 proteomes from sera of patients with primary Sjögrens syndrome and compare immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates and subjected to combined de novo amino acid sequencing and database matching. Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a molecular fingerprint of Ro60/La determinant spreading and suggesting that different forms of Ro60 antigen drive these responses. Sequencing of linked anti-Ro52 proteomes from individual patients and comparison with their anti-Ro60 partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide mapping provides insights into Ro/La autoantibody diversification and reveals serum-based molecular markers of humoral Ro60 autoimmunity.

Proteomic analysis of influenza haemagglutinin-specific antibodies following vaccination reveals convergent immunoglobulin variable region signatures

Analysis of the anti-haemagglutinin serum antibody proteome from six H1N1pdm09 influenza A vaccinated subjects demonstrated restricted IgG1 heavy chain species encoded by IGHV5-51 and IGHV3-7 gene families in 2 subjects and either IGHV5-51 or IGHV3-7 in 4 individuals. All subjects exhibited a dominant IGKV3-20 light chain, however 5 subjects also exhibited IGKV3-11 and IGKV4-1 families. Sequences were closely aligned with the matched germline sequence, with few shared mutations. This study illustrates the feasibility of using a proteomic approach to determine the expressed V region signatures of serum antibodies induced by vaccination.

Determination of an aspergillus fumigatus-specific immunoglobulin G reference range in an adult Omani population

Objectives The presence of abnormally high levels of Aspergillus fumigatus-specific immunoglobulin (Ig) G antibodies can serve as a diagnostic criterion for severe conditions like allergic bronchopulmonary and chronic pulmonary aspergillosis. This study aimed to determine a reference range of A. fumigatus-specific IgG levels within a healthy adult Omani population. Methods This study took place during November 2015 at the Sultan Qaboos University Hospital, Muscat, Oman. The sera of 125 healthy Omani blood donors were tested for A. fumigatus-specific IgG levels using an automated fluorescence enzyme immunoassay. Results Initially, the data were not normally distributed; however, log transformation and the exclusion of four outliers resulted in an acceptable Gaussian distribution. The reference range was 2.0-68.7 mgA/L at the 2.5th and 97.5th percentiles, respectively, with 90% confidence intervals of 2.0-3.0 mgA/L and 48.0-76.0 mgA/L, respectively. Conclusion The A. fumigatus-specific IgG reference range within a healthy adult Omani population was comparable to those reported in other populations.

The challenges of normative decision making in industries

The paper introduces decision analysis concept to help Press Company in Oman to select a printing machine. The main objective is to test the clarity of these concepts to industry and how easily decision makers (DM) grasp them. Although decision analysis has been discussed since 1976, we face some technical difficulties explaining these concepts to DM in the Press Company. One of the major concerns when applying normative approach was constructing a utility curve. Many industries apply “intuitive” decision making approach such as pros and cons, and experts opinion. Therefore, the methodology presented in the paper is to flip the coin and show that decision analysis normative approach “should” be applied to any decision making matter in the industry. We first introduces the decision frame, preferences, alternatives, and if any ambiguity surrounding the printing machine selection. By performing sensitivity analysis and overcoming technical difficulties, the Press Company was able to utilize decision analysis concepts.

Normative approach to Six Sigma project selection

This paper introduces the notion of expected utility and how to implement it in Six Sigma. Moreover, it intends to bridge the gap between process variation and the economic impact in order to have a clear view of economical consequences. It is agreed that the key for the success of any manufacturing firm is to select the most profitable project. There is a significant awareness in the Six Sigma community of the need for a tool that incorporates uncertainties, is data driven, and takes into account all financial aspects. Having an outstanding process quality is not necessarily an economical objective.