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Biomedical subjects

Samir Hanash

Publications and source records attributed to Samir Hanash.

At least 19 recordsLinked to original sources
PubMed2007

Ubiquitin COOH-terminal hydrolase 1: a biomarker of renal cell carcinoma associated with enhanced tumor cell proliferation and migration.

PURPOSE: Renal cell carcinoma (RCC) accounts for 2% to 3% of all malignancies. It represents one of the most radiation- and chemotherapy-resistant tumors and surgical resections are only effective in organ-defined disease. However, RCC is an immunogenic tumor with response rates to immunotherapies between 10% and 20% of the treated patients. Due to the currently inefficient therapies and the low 5-year survival rates of RCC patients, novel diagnostic, prognostic, and therapeutic markers are urgently needed for this disease. EXPERIMENTAL DESIGN: Proteome-based approaches were used to identify (a) differentially expressed proteins in RCC compared with normal kidney epithelium and (b) proteins that are able to induce an antibody response in RCC patients. Based on these experiments, a promising candidate was subsequently validated by reverse transcription-PCR, Western blot analyses, and immunohistochemistry. In addition, functional assays were done in generated transfectants. RESULTS: The ubiquitin COOH-terminal hydrolase L1 (UCHL1) was found to be differentially expressed in both RCC lesions and RCC cell lines and immunoreactive using patients' sera. UCHL1 expression was often down-regulated in primary RCC when compared with normal kidney epithelium but dependent on the RCC subtype, the von Hippel-Lindau phenotype, and the tumor grading. Moreover, the frequency and the level of UCHL1 expression were higher in metastases when compared with primary RCC lesions. Gain-of-function transfectants exhibited a significant higher proliferation and migration rate than UCHL1-negative RCC cells. CONCLUSIONS: UCHL1 expression seems to be associated with the metastatic phenotype of RCC and therefore might serve as potential biomarker for the diagnosis and prognosis of RCC patients.

Antineoplastic Agents↗
PubMed2006

Familial molar tissues due to mutations in the inflammatory gene, NALP7, have normal postzygotic DNA methylation.

An imprinting disorder has been believed to underlie the etiology of familial biparental hydatidiform moles (HMs) based on the abnormal methylation or expression of imprinted genes in molar tissues. However, the extent of the epigenetic defect in these tissues and the developmental stage at which the disorder begins have been poorly defined. In this study, we assessed the extent of abnormal DNA methylation in two HMs caused by mutations in the recently identified 19q13.4 gene, NALP7. We demonstrate normal postzygotic DNA methylation patterns at major repetitive and long interspersed nuclear elements (LINEs), genes on the inactive X-chromosome, three-cancer related genes, and CpG rich regions surrounding the PEG3 differentially methylated region (DMR). Our data provide a comprehensive assessment of DNA methylation in familial molar tissues and indicate that abnormal DNA methylation in these tissues is restricted to imprinted DMRs. The known role of NALP7 in apoptosis and inflammation pinpoints previously unrecognized pathways that could directly or indirectly underlie the abnormal methylation of imprinted genes in molar tissues.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation.

A subset of follicular thyroid carcinomas contains a balanced translocation, t(2;3)(q13;p25), that results in fusion of the paired box gene 8 (PAX8) and peroxisome proliferator-activated receptor gamma (PPARG) genes with concomitant expression of a PAX8-PPARgamma fusion protein, PPFP. PPFP is thought to contribute to neoplasia through a mechanism in which it acts as a dominant-negative inhibitor of wild-type PPARgamma. To better understand this type of follicular carcinoma, we generated global gene expression profiles using DNA microarrays of a cohort of follicular carcinomas along with other common thyroid tumors and used the data to derive a gene expression profile characteristic of PPFP-positive tumors. Transient transfection assays using promoters of four genes whose expression was highly associated with the translocation showed that each can be activated by PPFP. PPFP had unique transcriptional activities when compared with PAX8 or PPARgamma, although it had the potential to function in ways qualitatively similar to PAX8 or PPARgamma depending on the promoter and cellular environment. Bioinformatics analyses revealed that genes with increased expression in PPFP-positive follicular carcinomas include known PPAR target genes; genes involved in fatty acid, amino acid, and carbohydrate metabolism; micro-RNA target genes; and genes on chromosome 3p. These results have implications for the neoplastic mechanism of these follicular carcinomas.

Adenocarcinoma, Follicular↗
PubMed2006

Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans.

Hydatidiform mole (HM) is an abnormal human pregnancy with no embryo and cystic degeneration of placental villi. We report five mutations in the maternal gene NALP7 in individuals with familial and recurrent HMs. NALP7 is a member of the CATERPILLER protein family involved in inflammation and apoptosis. NALP7 is the first maternal effect gene identified in humans and is also responsible for recurrent spontaneous abortions, stillbirths and intrauterine growth retardation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Quantitative analysis of acrylamide labeled serum proteins by LC-MS/MS.

Isotopic labeling of cysteine residues with acrylamide was previously utilized for relative quantitation of proteins by MALDI-TOF. Here, we explored and compared the application of deuterated and (13)C isotopes of acrylamide for quantitative proteomic analysis using LC-MS/MS and high-resolution FTICR mass spectrometry. The method was applied to human serum samples that were immunodepleted of abundant proteins. Our results show reliable quantitation of proteins across an abundance range that spans 5 orders of magnitude based on ion intensities and known protein concentration in plasma. The use of (13)C isotope of acrylamide had a slightly greater advantage relative to deuterated acrylamide, because of shifts in elution of deuterated acrylamide relative to its corresponding nondeuterated compound by reversed-phase chromatography. Overall, the use of acrylamide for differentially labeling intact proteins in complex mixtures, in combination with LC-MS/MS provides a robust method for quantitative analysis of complex proteomes.

Acrylamides↗
PubMed2006

Cleavage of endoplasmic reticulum proteins in hepatocellular carcinoma: Detection of generated fragments in patient sera.

BACKGROUND & AIMS: In the past decade, there has been a rising incidence of hepatocellular carcinoma (HCC) and a progressive increase in HCC-related mortality in the United States and Western Europe. The poor survival of patients with HCC is largely related to the lack of reliable tools for early diagnosis. METHODS: We have applied proteomics tools to the comparative analysis of protein profiles between HCC and adjacent nontumor tissues as a means for discovering novel molecular markers. RESULTS: Forty-seven protein spots that showed reproducible variation were identified by mass spectrometry, corresponding to 23 distinct genes. A positive correlation between transcript and protein level variations was observed for only 7 out of the 23 genes. Proteolytic cleavage accounted for the discrepancies between messenger RNA and protein level changes for 7 genes including calreticulin, PDIA3, PDI, and GRP78. We detected a fragment of each of these 4 endoplasmic reticulum proteins in the culture supernatant of the PLC-PRF5 hepatoma cell line, suggesting that their cleavage leads to release of selected cleaved products in the extracellular compartment. We also detected calreticulin and PDIA3 cleavage products in sera of patients with HCC. A statistically highly significant difference in calreticulin and PDIA3 fragment serum levels between patients with HCC and healthy individuals was observed. Amounts of calreticulin and PDIA3 fragments were also significantly different between patients with HCC and at-risk patients (patients with chronic hepatitis or cirrhosis). CONCLUSIONS: Specific isoforms in general and cleavage products in particular should therefore be further evaluated as new markers for HCC.

Biomarkers, Tumor↗
PubMed2006

High-throughput genomic technology in research and clinical management of breast cancer. Plasma-based proteomics in early detection and therapy.

Protein-based breast cancer biomarkers are a promising resource for breast cancer detection at the earliest and most treatable stages of the disease. Plasma is well suited to proteomic-based methods of biomarker discovery because it is easily obtained, is routinely used in the diagnosis of many diseases, and has a rich proteome. However, due to the vast dynamic range in protein concentration and the often uncertain tissue and cellular origin of plasma proteins, proteomic analysis of plasma requires special consideration compared with tissue and cultured cells. This review briefly touches on the search for plasma-based protein biomarkers for the early detection and treatment of breast cancer.

Biomarkers, Tumor↗
PubMed2005

Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis.

Thyroid cancer poses a significant clinical challenge, and our understanding of its pathogenesis is incomplete. To gain insight into the pathogenesis of papillary thyroid carcinoma, transcriptional profiles of four normal thyroids and 51 papillary carcinomas (PCs) were generated using DNA microarrays. The tumors were genotyped for their common activating mutations: BRAF V600E point mutation, RET/PTC1 and 3 rearrangement and point mutations of KRAS, HRAS and NRAS. Principal component analysis based on the entire expression data set separated the PCs into three groups that were found to reflect tumor morphology and mutational status. By combining expression profiles with mutational status, we defined distinct expression profiles for the BRAF, RET/PTC and RAS mutation groups. Using small numbers of genes, a simple classifier was able to classify correctly the mutational status of all 40 tumors with known mutations. One tumor without a detectable mutation was predicted by the classifier to have a RET/PTC rearrangement and was shown to contain one by fluorescence in situ hybridization analysis. Among the mutation-specific expression signatures were genes whose differential expression was a direct consequence of the mutation, as well as genes involved in a variety of biological processes including immune response and signal transduction. Expression of one mutation-specific differentially expressed gene, TPO, was validated at the protein level using immunohistochemistry and tissue arrays containing an independent set of tumors. The results demonstrate that mutational status is the primary determinant of gene expression variation within these tumors, a finding that may have clinical and diagnostic significance and predicts success for therapies designed to prevent the consequences of these mutations.

Base Sequence↗
PubMed2005

CDX2 polymorphisms, RNA expression, and risk of colorectal cancer.

In adult mammals, CDX2 acts as a transcription factor and is expressed in intestinal epithelial cells. Down-regulation of CDX2 is frequently observed in colorectal cancer, suggesting its loss may cause dedifferentiation of gastrointestinal epithelial cells. However, it is not clear whether inherited variants of CDX2 are associated with risk of colorectal cancer. Using epidemiologic data and tumors from a population-based case-control study in Israel, we identified novel single nucleotide polymorphisms (SNPs) by resequencing 35 cases, compared genotype and haplotype frequencies in 455 matched pairs, and characterized the tumor characteristics of all 455 cases by microsatellite instability analysis, in addition to a partially overlapping set of 201 frozen tumors with expression profiling data (82/201) from the same study. Nine polymorphisms were identified in the 35 cases, and none of the SNPs or haplotypes were associated with risk of colorectal cancer in the 455 matched pairs. These variants were not associated with CDX2 expression in the 83 subjects with expression data. We evaluated subject and tumor characteristics in the 201 subjects with CDX2 tumor expression data. Reduced CDX2 expression was associated with tumor location (right sided), poor differentiation, high microsatellite instability status, and a positive first-degree family history. We conclude that it is unlikely that common CDX2 variants account for a measurable fraction of susceptibility to colorectal cancer in this population. However, CDX2 expression levels were strongly associated with microsatellite instability and tumor location in the gastrointestinal tract, consistent with a possible role in the specification of gastrointestinal epithelial cell fate in humans.

Aged↗
PubMed2005

Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability.

Hox genes encode transcription factors that regulate the morphogenesis of developing embryos. In mammals, knowledge of the genetic pathways, including the possible direct or indirect targets, regulated by HOX proteins is extremely limited. To identify the downstream genes regulated by posterior HOX proteins, we expressed HOXA13 in mouse embryonic fibroblasts lacking paralog group 13 expression using a bicistronic HOXA13/EGFP retroviral vector. Microarray analysis identified 68 genes with significant, reproducible RNA expression changes (50 activated; 18 repressed) in stable HOXA13-expressing cells. Genes with the GO annotation terms "extracellular matrix" and "basement membrane" were greatly overrepresented, and several were shown to be regulated by HOX proteins in other studies. Among the genes strongly activated by HOXA13 were Enpp2, a bifunctional enzyme known to modulate tumor and normal cell motility and which is expressed in precartilaginous condensations; Fhl1, a transcription factor implicated in muscle cell differentiation and development; and M32486, a putative integral membrane molecule expressed in the female reproductive tract. Expression differences in the HOXA13-expressing cells were confirmed for selected downstream genes using semi-quantitative RT-PCR, and in vivo coexpression with Hoxa13 in the limb interdigital mesenchyme was demonstrated for many. For two candidates, Igfbp4 and Fstl, interdigital limb bud expression was reduced in Hoxa13 mutants. To explore whether paralogous and nonparalogous HOX proteins could regulate the same genes, we created new HOX cell lines and examined the expression of selected genes identified by the HOXA13 screen. HOXD13 similarly activated/repressed 6 tested candidates, demonstrating that multiple downstream genetic pathways may be regulated by paralog HOX proteins. In contrast, HOXA9 was only able to repress expression of some gene targets. A HOXD13 mutant, HOXD13(IQN >)(AAA), incapable of monomeric DNA-binding, activated the expression of 5 HOXA13-upregulated genes; but was incapable of repressing the expression of Ngef and Casp8ap2. Our results suggest that HOX protein-protein interactions without direct HOX DNA-binding may play a larger role in HOX transcriptional regulation than generally assumed, and DNA-binding appears critical for repression.

Animals↗
PubMed2005

Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.

PURPOSE: Ovarian and uterine carcinomas manifest several differentiation patterns resembling those seen in nonneoplastic epithelia of the gynecologic tract. Specific oncogene and tumor suppressor gene defects have been associated with particular differentiation patterns in carcinomas arising in either the uterus or ovary. For instance, ovarian and uterine carcinomas with endometrioid differentiation frequently show beta-catenin mutations. Whereas type of differentiation is considered in the treatment of uterine carcinomas, it does not presently contribute to decisions about treatment of ovarian carcinomas. A widely accepted view is that the accumulation of specific gene defects and gene expression changes underlies phenotypic traits of cancers, including their response to treatment. EXPERIMENTAL DESIGN: Using oligonucleotide microarrays to assess gene expression in 103 primary ovarian and uterine carcinomas, we sought to address whether organ of origin or type of differentiation (histotype; endometrioid versus serous) had a more substantial effect on gene expression patterns. RESULTS: We found that effects on gene expression due to organ of origin and histotype are similar in magnitude and are parallel in that organ effects are similar in the two histotypes and histotype effects are similar in the two organs. In addition, ovarian and uterine endometrioid adenocarcinomas with beta-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects. CONCLUSIONS: Our results illustrate how organ of origin, type of differentiation, and specific molecular defects all contribute to gene expression in the most common types of ovarian and uterine cancers. The findings also imply gene expression data will be of value for stratifying ovarian cancer patients for new treatment approaches.

Cell Differentiation↗
PubMed2005

Comparison of seven methods for producing Affymetrix expression scores based on False Discovery Rates in disease profiling data.

BACKGROUND: A critical step in processing oligonucleotide microarray data is combining the information in multiple probes to produce a single number that best captures the expression level of a RNA transcript. Several systematic studies comparing multiple methods for array processing have used tightly controlled calibration data sets as the basis for comparison. Here we compare performances for seven processing methods using two data sets originally collected for disease profiling studies. An emphasis is placed on understanding sensitivity for detecting differentially expressed genes in terms of two key statistical determinants: test statistic variability for non-differentially expressed genes, and test statistic size for truly differentially expressed genes. RESULTS: In the two data sets considered here, up to seven-fold variation across the processing methods was found in the number of genes detected at a given false discovery rate (FDR). The best performing methods called up to 90% of the same genes differentially expressed, had less variable test statistics under randomization, and had a greater number of large test statistics in the experimental data. Poor performance of one method was directly tied to a tendency to produce highly variable test statistic values under randomization. Based on an overall measure of performance, two of the seven methods (Dchip and a trimmed mean approach) are superior in the two data sets considered here. Two other methods (MAS5 and GCRMA-EB) are inferior, while results for the other three methods are mixed. CONCLUSIONS: Choice of processing method has a major impact on differential expression analysis of microarray data. Previously reported performance analyses using tightly controlled calibration data sets are not highly consistent with results reported here using data from human tissue samples. Performance of array processing methods in disease profiling and other realistic biological studies should be given greater consideration when comparing Affymetrix processing methods.

Algorithms↗
PubMed2005

Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays.

A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study.

Adenocarcinoma↗
PubMed2005

CDX2-regulated expression of iron transport protein hephaestin in intestinal and colonic epithelium.

BACKGROUND & AIMS: The homeobox transcription factor CDX2 has a key role in intestinal development and differentiation. Mice heterozygous for Cdx2 inactivation develop colonic polyps with epithelial cells showing gastric or squamous differentiation. Loss of CDX2 expression is seen in some poorly differentiated colon carcinomas in humans. Conversely, ectopic CDX2 expression in the stomach of transgenic mice promotes intestinal metaplasia, and CDX2 expression often is seen in intestinal metaplasia in stomach and esophagus. To enhance knowledge of CDX2 function, we sought to define CDX2-regulated genes. METHODS: HT-29 and WiDr colorectal cancer (CRC) cells with low endogenous CDX2 expression were transduced with a CDX2 expression vector, and gene expression changes were assessed by microarrays. RESULTS: The gene for ceruloplasmin-related iron transport protein hephaestin (HEPH) was induced by CDX2 in HT-29 and WiDr. In other CRC lines and human and mice tissues, endogenous HEPH expression was linked to CDX2 expression. Activation of CDX2 rapidly induced HEPH expression, and RNA interference-mediated inhibition of CDX2 led to lower HEPH expression. Studies with HEPH reporter gene constructs and chromatin-immunoprecipitation approaches suggested that CDX2 directly regulates HEPH transcription. In CRC cells, CDX2 induction suppressed intracellular iron levels, consistent with the view that HEPH regulates iron export. CDX2 expression was modulated in response to changes in intracellular iron levels, implying a regulatory pathway in which increased iron levels lead to increased expression of CDX2 and HEPH and enhanced iron export. CONCLUSIONS: CDX2 has a key role in regulating HEPH expression and iron levels in intestinal cells.

Animals↗
PubMed2004

Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: The survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor-associated macrophage content. The authors hypothesized that tumor-associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens. METHODS: Oligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high-density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival. RESULTS: Monocyte chemoattractant protein 1 was up-regulated significantly in tumors compared with normal mucosa (P=0.0025; fold change=1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P <0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P <0.0001), extracapsular lymph node spread (P=0.0001), and advanced clinical disease stage (P=0.0002). When it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P <0.0001). CONCLUSIONS: Primary tumor macrophage content is a strong predictor of tumor aggressiveness in HNSCC.

Adult↗
PubMed2004

Molecular profiling and the identification of genes associated with metastatic oral cavity/pharynx squamous cell carcinoma.

OBJECTIVE: To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors. DESIGN: Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin. SUBJECTS: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy. RESULTS: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change > or =1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change > or =1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 alpha-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P=.003). CONCLUSIONS: Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.

Carcinoma, Squamous Cell↗
PubMed2004

Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors.

OBJECTIVE: Generalized DNA hypomethylation contributes to altered T cell function and gene expression in systemic lupus erythematosus (SLE). Some of the overexpressed genes participate in the disease process, but the full repertoire of genes affected is unknown. Methylation-sensitive T cell genes were identified by treating T cells with the DNA methyltransferase inhibitor 5-azacytidine and comparing gene expression with oligonucleotide arrays. CD70, a costimulatory ligand for B cell CD27, was one gene that reproducibly increased. We then determined whether CD70 is overexpressed on T cells treated with other DNA methylation inhibitors and on SLE T cells, and determined its functional significance. METHODS: Oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction, and flow cytometry were used to compare CD70 expression in T cells treated with 2 DNA methyltransferase inhibitors (5-azacytidine and procainamide) and 3 ERK pathway inhibitors known to decrease DNA methyltransferase expression (U0126, PD98059, and hydralazine). The consequences of CD70 overexpression were tested by coculture of autologous T and B cells with and without anti-CD70 and measuring IgG production by enzyme-linked immunosorbent assay. The results were compared with those of T cells from lupus patients. RESULTS: SLE T cells and T cells treated with DNA methylation inhibitors overexpressed CD70 and overstimulated B cell IgG production. The increase in IgG synthesis was abrogated by anti-CD70. CONCLUSION: SLE T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. This increased B cell costimulation and subsequent immunoglobulin overproduction may contribute to drug-induced and idiopathic lupus.

Adult↗