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1.  Biomarker Discovery for Lupus Nephritis Through Longitudinal Urine Proteomics 
Kidney international  2008;74(6):799-807.
Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE). Treatment often requires the use of immunosuppression, and may be associated with severe side effects. The ability to predict relapse, relapse severity, and recovery could be used to more effectively implement therapy and reduce toxicity. We postulated that a proteomic analysis of the low-molecular weight urine proteome using serial urine samples obtained before, during, and after SLE nephritis flares would demonstrate potential biomarkers of SLE renal flare. This study was undertaken to test our hypothesis.
Urine from 25 flare cycles of 19 WHO Class III, IV, and V SLE nephritis patients was used. Urine samples included a baseline, and pre-flare, flare, and post-flare specimens. The urines were fractionated to remove proteins larger than 30 kDa, and spotted onto weak cation exchanger (CM10) protein chips for analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS).
SELDI-TOF MS screening showed 176 protein ions between 2-20 kDa of which 27 were found to be differentially-expressed between specific flare intervals. On-chip peptide sequencing by integrated tandem mass spectrometry was used to positively identify selected differentially-expressed protein ions. The identified proteins included the 20 and 25 amino acid isoforms of hepcidin, a fragment of α1-antitrypsin, and an albumin fragment. Hepcidin 20 increased 4 months pre-flare and returned to baseline at renal flare, whereas hepcidin 25 decreased at renal flare and returned to baseline 4 months post-flare.
Using SELDI-TOF urine protein profiling in lupus nephritis, several candidate biomarkers of renal flare were found. To verify these candidates as true biomarkers, further identification and validation are needed in an independent SLE cohort.
doi:10.1038/ki.2008.316
PMCID: PMC2614389  PMID: 18596723
lupus nephritis; biomarker; SELDI
2.  Association of Smoking Behavior with an Odorant Receptor Allele Telomeric to the Human Major Histocompatibility Complex 
Genetic testing  2008;12(4):481-486.
Smoking behavior has been associated in two independent European cohorts with the most common Caucasian human leukocyte antigen (HLA) haplotype (A1-B8-DR3). We aimed to test whether polymorphic members of the two odorant receptor (OR) clusters within the extended HLA complex might be responsible for the observed association, by genotyping a cohort of Hungarian women in which the mentioned association had been found. One hundred and eighty HLA haplotypes from Centre d’Etude du Polymorphisme Humain families were analyzed in silico to identify single-nucleotide polymorphisms (SNPs) within OR genes that are in linkage disequilibrium with the A1-B8-DR3 haplotype, as well as with two other haplotypes indirectly linked to smoking behavior. A nonsynonymous SNP within the OR12D3 gene (rs3749971T) was found to be linked to the A1-B8-DR3 haplotype. This polymorphism leads to a 97Thr → Ile exchange that affects a putative ligand binding region of the OR12D3 protein. Smoking was found to be associated in the Hungarian cohort with the rs3749971T allele (p = 1.05×10−2), with higher significance than with A1-B8-DR3 (p = 2.38×10−2). Our results link smoking to a distinct OR allele, and demonstrate that the rs3749971T polymorphism is associated with the HLA haplotype-dependent differential recognition of cigarette smoke components, at least among Caucasian women.
doi:10.1089/gte.2008.0029
PMCID: PMC2635552  PMID: 18939942

Results 1-2 (2)