Mitochondrial Dysfunction and Fatigue in Sjögren's Disease.

Objectives: Sjögren's disease (SjD) is a common exocrine disorder typified by chronic inflammation and dryness, but also profound fatigue, suggesting a pathological basis in cellular bioenergetics. In healthy states, damaged or dysfunctional mitochondrial components are broken down and recycled by mitophagy, a specialized form of autophagy. In many autoimmune disorders, however, evidence suggests that dysfunctional mitophagy allows poorly functioning mitochondria to persist and contribute to a cellular milieu with elevated reactive oxygen species.

Ovarian antibodies among SLE women with premature menopause after cyclophosphamide.

Background: Women with systemic lupus erythematosus (SLE) are at risk of premature ovarian failure when treated with cyclophosphamide. This risk is increased when autoimmune thyroid disease is present. We undertook this study to determine whether the presence of ovarian autoimmunity also increased the risk of early ovarian failure among women receiving cyclophosphamide.

Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis.

Ninety percent of systemic lupus erythematosus (SLE) patients are women. X chromosome-dosage increases susceptibility to SLE and primary Sjögren's syndrome (pSS). Chromosome X open reading frame 21 escapes X-inactivation and is an SLE risk gene of previously unknown function.

American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than European Americans and African Americans.

Objective: To describe the clinical and serologic manifestations of Sjögren's syndrome (SS) in ethnic groups of the US.

Methods: This was a cross-sectional study of 648 patients with primary SS: 20 African American (AA), 164 American Indian (AI), 426 European American (EA), and 38 patients of other races evaluated in a multidisciplinary Sjögren's International Collaborative Clinical Alliance research clinic.

Results: AA subjects comprised 3.

Lysosomal pH Is Regulated in a Sex Dependent Manner in Immune Cells Expressing .

and both contain risk alleles for systemic lupus erythematosus (SLE) and Sjögren's syndrome (pSS). The former escapes X inactivation. Our group predicts specific endolysosomal-dependent immune responses are driven by the protein products of these genes, which form a complex at the endolysosomal surface.

Single-Cell High-Resolution Detection and Quantification of Protein Isoforms Differing by a Single Charge Unit.

Isoelectric focusing (IEF) is an electrophoretic technique that enables the separation of proteins based on their isoelectric points. Until recently, this valuable method was not feasible for single-cell applications, which are necessary to interrogate heterogeneous cell populations. Herein we highlight a recently published method enabling the analysis of single-cell proteomics, which utilizes microfluidics coupled with IEF, photocapture, and immunoprobing of the protein in the same micro-gel, which can be stripped and reprobed multiple times.

Prognostic value of Sjögren's syndrome autoantibodies.

Sjögren's syndrome is in part considered an autoimmune disease because patient sera contain antibodies binding self-structures. In fact, in addition to anti-Ro (or SSA) and anti-La (or SSB), which are included in the classification criteria, there are a wide variety of autoantibodies found among these patients. We reviewed English-language MEDLINE sources.

Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N-Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren's Syndrome.

Objective: To better understand the role of B cells, the potential mechanisms responsible for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's syndrome (SS), this study explored patterns of selection pressure and sites of N-glycosylation acquired by somatic mutation (acN-glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated from the minor salivary glands of patients with SS and non-SS control patients with sicca symptoms.

Methods: A novel method to produce and characterize recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates was applied to concurrently probe expressed genes (all heavy- and light-chain isotypes as well as any other gene of interest not related to immunoglobulin) in the labial salivary glands of patients with SS and non-SS controls. V regions were amplified by reverse transcription-polymerase chain reaction, sequenced, and analyzed for the incidence of N-glycosylation and selection pressure.

Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome.

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome.

Anti-La positive, anti-Ro negative subset of primary Sjögren's syndrome: anti-La is a reality but is the disease?

Objectives: To characterise the serological and clinical findings in primary Sjögren's syndrome in which anti-La was found without anti-Ro. We hypothesised that a significant portion of these are falsely negative for anti-Ro60.

Methods: Twenty-nine sera from primary Sjögren's syndrome patients were tested for antibodies directed against La and Ro.

Antiadrenergic autoimmunity in postural tachycardia syndrome.

Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).

Methods And Results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro.

Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes.

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

Objective: More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls.

Methods: All subjects in this study were female.

Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment.

Objectives: Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)).

Association between Secondary and Primary Sjögren's Syndrome in a Large Collection of Lupus Families.

Objective. Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families.

T Cell ELISPOT: For the Identification of Specific Cytokine-Secreting T Cells.

The ELISPOT is a powerful functional assay used to detect biological activity and immunological secretions from immune cells. In this chapter, we specifically discuss T cell ELISPOT methods for the detection of secreted cytokines. A detailed protocol is given enabling the detection of interferon gamma-secreting CD8(+) T cells and/or peripheral blood mononuclear cells following their isolation and polyclonal activation.

B-Cell ELISPOT: For the Identification of Antigen-Specific Antibody-Secreting Cells.

The B-cell ELISPOT assay is a sensitive tool that can be utilized to measure total immunoglobulin (Ig) and antigen-specific antibody-secreting cells. Typically, membrane-bound antigen enables binding of antibody secreted by B-cells. Bound antibody is then detected by using an anti-Ig antibody and a colorimetric substrate, resulting in colored spots on the membrane that can be easily enumerated.

Antibody-secreting cell specificity in labial salivary glands reflects the clinical presentation and serology in patients with Sjögren's syndrome.

Objective: The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)-derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.

Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjögren's syndrome.

Objective: Primary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS.

Methods: A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicity-matched healthy controls.

Systematic classification of non-coding RNAs by epigenomic similarity.

Background: Even though only 1.5% of the human genome is translated into proteins, recent reports indicate that most of it is transcribed into non-coding RNAs (ncRNAs), which are becoming the subject of increased scientific interest. We hypothesized that examining how different classes of ncRNAs co-localized with annotated epigenomic elements could help understand the functions, regulatory mechanisms, and relationships among ncRNA families.

Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naïve CD4+ T cells from lupus patients.

Systemic lupus erythematosus is an autoimmune disease characterized by multi-system involvement and autoantibody production. Abnormal T cell DNA methylation and type-I interferon play an important role in the pathogenesis of lupus. We performed a genome-wide DNA methylation study in two independent sets of lupus patients and matched healthy controls to characterize the DNA methylome in naïve CD4+ T cells in lupus.

GFP affects human T cell activation and cytokine production following in vitro stimulation.

There are many Green Fluorescent Proteins (GFPs) originating from diverse species that are invaluable to cell biologists today because of their ability to provide experimental visualization of protein expression. Since their initial discovery, they have been modified and improved to provide more stable variants with emission ranges spanning a wide array of colors. Due to their ease of expression both in-vitro and in-vivo, they are an attractive choice for use as markers in molecular biology.

Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse.

Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis.