-
Autoimmunity Reviews Dec 2023Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring... (Review)
Review
Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring disease activity and treatment response. Therefore, clinicians rely on them to diagnose and adjust medication and treatment strategies for SLE patients. However, the use of anti-dsDNA antibodies is not free from controversy. Part of this controversy stems from the fact that anti-dsDNA antibodies are found in several disorders, besides SLE. In addition to this, anti-dsDNA antibodies are a heterogeneous group of antibodies, and their determination still lacks proper standardization. Moreover, anti-dsDNA testing specificity and diagnostic performance change depending on the population under study. These and other issues result in inconsistency and encumber the clinical use of anti-dsDNA antibodies. A panel of medical laboratory and clinical experts on SLE discussed such issues based on their clinical experience in a first meeting, establishing a series of recommendations. The proceedings of this first meeting, plus an exhaustive review of the literature, were used to compose a paper draft. The panel subsequently discussed and refined this draft in a second meeting, the result of which is this paper. This document is relevant to clinical laboratories as it guides to improving diagnosis and monitoring of SLE. Simultaneously, it will help laboratories compile more informative reports, not limited to a mere number. It is also relevant to clinical doctors who wish to better understand laboratory methods so that they can do a more efficient, better-aimed laboratory test ordering.
Topics: Humans; Autoantibodies; Follow-Up Studies; Lupus Erythematosus, Systemic; Antibodies, Antinuclear
PubMed: 37967782
DOI: 10.1016/j.autrev.2023.103479 -
Cancer Genomics & Proteomics 2017Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an... (Review)
Review
BACKGROUND/AIM
Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an Autoantibody Profiling System (APS) and quantify the levels in plasma of donors with/without breast cancer.
MATERIALS AND METHODS
Plasma from nine female donors diagnosed with breast cancer (test group) and nine matched donors with no personal history of cancer (reference group) were screened with an APS containing probes for 30 autoantibodies. Autoantibody levels ≥1.5 times the mean concentration of the group were considered elevated, and test/reference ratios ≥1.3 were considered higher in the test group compared to the reference group.
RESULTS
Twenty percent of the probes detected elevated levels of autoantibodies against proteins involved in different cancer mechanisms. Amongst these, the levels of autoantibodies against interleukin 29 (IL29), osteoprotegerin (OPG), survivin (SUR), growth hormone (GRH) and resistin (RES) were significantly higher in the cancer group compared to the reference group (p<0.05), whereas the level of autoantibody against cytotoxic T-lymphocyte associated antigen-4 (CTLA4) was not significantly different between the two groups (p=0.38).
CONCLUSION
Disease-relevant autoantibodies were detected in the plasma of patients with breast cancer and donors without breast cancer. This means that identifying the type and level of autoantibodies in samples will be important in determining their significance in the disease process. A microtiter plate-based array system could be a fast and inexpensive screening method for identifying and quantifying autoantibodies in human plasma.
Topics: Adult; Autoantibodies; Breast Neoplasms; Female; Humans; Mass Screening; Young Adult
PubMed: 29109092
DOI: 10.21873/cgp.20052 -
Nature Reviews. Neurology Sep 2020A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy,... (Review)
Review
A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy, patients with these neuroglial surface autoantibody (NSAb)-mediated diseases often experience clinical relapse, high rates of long-term morbidity and adverse effects from the available medications. Fundamentally, the autoantigen-specific B cell lineage leads to production of the pathogenic autoantibodies. These autoantigen-specific B cells have been consistently identified in the circulation of patients with NSAb-mediated diseases, accompanied by high serum levels of autoantigen-specific antibodies. Early evidence suggests that these cells evade well-characterized B cell tolerance checkpoints. Nearer to the site of pathology, cerebrospinal fluid from patients with NSAb-mediated diseases contains high levels of autoantigen-specific B cells that are likely to account for the intrathecal synthesis of these autoantibodies. The characteristics of their immunoglobulin genes offer insights into the underlying immunobiology. In this Review, we summarize the emerging knowledge of B cells across the NSAb-mediated diseases. We review the evidence for the relative contributions of germinal centres and long-lived plasma cells as sources of autoantibodies, discuss data that indicate migration of B cells into the CNS and summarize insights into the underlying B cell pathogenesis that are provided by therapeutic effects.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmune Diseases; B-Lymphocytes; Central Nervous System Diseases; Humans; Immunotherapy
PubMed: 32724223
DOI: 10.1038/s41582-020-0381-z -
Clinical and Experimental Immunology Dec 1979Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune... (Review)
Review
Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune liver diseases, viral infections, certain cancers, heroin addicts and female infertility. SMA from patients with chronic active hepatitis reacts with many muscle and 'non-muscle' tissues while SMA from patients with other diseases usually reacts only with smooth muscle. These differences in immunofluorescent staining reactions suggest that SMA is a heterogeneous group of autoantibodies reactive with different smooth muscle autoantigens. As further evidence for this are findings that broad-reacting SMA can be absorbed out by actin, whereas autoantibodies reactive only with smooth muscle cannot, and that different SMAs give different immunofluorescent staining patterns using fibroblasts in tissue culture. Such staining patterns correspond to reactivity with either microfilaments, microtubules or intermediate filaments, ubiquitous cytoplasmic structures which make up the 'cytoskeleton'. Autoantibodies to actin-like microfilaments appear specific for chronic active hepatitis, autoantibodies to microtubules occur in infectious mononucleosis whereas autoantibodies to intermediate filaments occur in infectious hepatitis, chickenpox, measles and mumps. Predictably, future studies will show that presence of SMA with specificities for other proteins in the three types of cytoplasmic filaments, and given more information on antigenicity of the proteins and pathogenicity of the corresponding autoantibodies.
Topics: Actins; Animals; Antibody Specificity; Antigens; Autoantibodies; Autoantigens; Autoimmune Diseases; Cytoskeleton; Epitopes; Humans; Kidney; Muscle, Smooth; Rabbits; Rats
PubMed: 93995
DOI: No ID Found -
Frontiers in Immunology 2022Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA),... (Review)
Review
Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA), and susceptibility to this disease, has been studied for over three decades. The genetic susceptibility to AIH is believed to be different in the two subtypes of the disease, AIH type 1 and AIH type 2. Type 1 AIH has anti-smooth muscle and anti-nuclear antibodies as its main markers, while those of type 2 AIH are the anti-liver/kidney microsome type 1 and anti-liver cytosol type 1 antibodies. The anti-soluble liver antigen/liver-pancreas antibodies, which, in addition to being present in both subtypes, mark an important number of patients without serological markers. Therefore, a third type of disease is questionable. The vast majority of immunogenetic studies compare the differences between the two main types and make no difference between which antibodies are present to define the subtype. This review seeks to analyze what was most important published in the AIH in this context, trying to relate the HLA alleles according to the AIH marker autoantibodies.
Topics: Humans; Hepatitis, Autoimmune; Genetic Predisposition to Disease; Autoantibodies; Antibodies, Antinuclear; Biomarkers
PubMed: 36311739
DOI: 10.3389/fimmu.2022.1032591 -
Frontiers in Immunology 2022Autoantibodies are found in various pathological conditions such as autoimmune diseases, infectious diseases, and malignant tumors. However their clinical implications...
Autoantibodies are found in various pathological conditions such as autoimmune diseases, infectious diseases, and malignant tumors. However their clinical implications have not yet been fully elucidated. Herein, we conducted proteome-wide autoantibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX) maintaining their three-dimensional structure. A total of 565 autoantibodies were identified from the sera of three representative inflammatory disorders (systemic sclerosis, psoriasis, and cutaneous arteritis). Each autoantibody level either positively or negatively correlated with serum levels of C-reactive protein, the best-recognized indicator of inflammation. In particular, we discovered total levels of a subset of autoantibodies correlates with the severity of clinical symptoms. From the sera of malignant melanoma, 488 autoantibodies were detected. Notably, patients with metastases had increased overall autoantibody production compared to those with tumors limiting to the primary site. Collectively, proteome-wide screening of autoantibodies using the proteome can reveal the "autoantibody landscape" of human subjects and may provide novel clinical biomarkers.
Topics: Autoantibodies; Autoimmune Diseases; Biomarkers; Humans; Protein Array Analysis; Proteome
PubMed: 35603173
DOI: 10.3389/fimmu.2022.893086 -
Endocrine Practice : Official Journal... Jul 2023Autoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using...
OBJECTIVE
Autoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn).
METHODS
Serial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo.
RESULTS
In contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis.
CONCLUSION
Targeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD.
Topics: Humans; Infant, Newborn; Antibodies, Monoclonal; Autoantibodies; Graves Disease; Immunoglobulins, Thyroid-Stimulating; Long-Acting Thyroid Stimulator; Receptors, Thyrotropin; Thyrotropin
PubMed: 37080298
DOI: 10.1016/j.eprac.2023.04.002 -
Frontiers in Immunology 2023Recent studies report high-titer anti-dense fine speckled 70 (DFS70) autoantibodies in persons with inflammatory conditions, but the clinical significance remains...
OBJECTIVE
Recent studies report high-titer anti-dense fine speckled 70 (DFS70) autoantibodies in persons with inflammatory conditions, but the clinical significance remains unclear. Our goals were to estimate anti-DFS70 autoantibody prevalence, identify correlates, and assess time trends.
METHODS
Serum antinuclear antibodies (ANA) were measured by indirect immunofluorescence assay on HEp-2 cells in 13,519 participants ≥12 years old from three time periods (1988-1991, 1999-2004, 2011-2012) of the National Health and Nutrition Examination Survey. ANA-positive participants with dense fine speckled staining were evaluated for anti-DFS70 antibodies by enzyme-linked immunosorbent assay. We used logistic models adjusted for survey-design variables to estimate period-specific anti-DFS70 antibody prevalence in the US, and we further adjusted for sex, age, and race/ethnicity to identify correlates and assess time trends.
RESULTS
Women were more likely than men (odds ratio (OR)=2.97), black persons were less likely than white persons (OR=0.60), and active smokers were less likely than nonsmokers (OR=0.28) to have anti-DFS70 antibodies. The prevalence of anti-DFS70 antibodies increased from 1.6% in 1988-1991 to 2.5% in 1999-2004 to 4.0% in 2011-2012, which corresponds to 3.2 million, 5.8 million, and 10.4 million seropositive individuals, respectively. This increasing time trend in the US population (P<0.0001) was modified in some subgroups and was not explained by concurrent changes in tobacco smoke exposure. Some, but not all, anti-DFS70 antibody correlates and time trends resembled those reported for total ANA.
CONCLUSION
More research is needed to elucidate anti-DFS70 antibody triggers, their pathologic or potentially protective influences on disease, and their possible clinical implications.
Topics: Female; Humans; Male; Adaptor Proteins, Signal Transducing; Antibodies, Antinuclear; Autoantibodies; Nutrition Surveys; Prevalence; United States
PubMed: 37426660
DOI: 10.3389/fimmu.2023.1186439 -
Medicine Jan 2010Ethnicity and environmental factors could be involved in the heterogeneity of systemic lupus erythematosus (SLE). We conducted this study to define clinical and...
Ethnicity and environmental factors could be involved in the heterogeneity of systemic lupus erythematosus (SLE). We conducted this study to define clinical and serologic correlations and autoantibody clusters in SLE patients in South China. We retrospectively reviewed the records of 917 patients with SLE admitted to our hospital between January 2005 and June 2008. We found the following associations between autoantibodies and clinical manifestations to be statistically significant: anti-double-stranded DNA (anti-dsDNA) with higher prevalence of renal disorder, leukopenia, and anemia; anti-Sm with higher prevalence of malar rash/discoid rash, pericarditis, and leukopenia; anti-ribonucleoprotein (anti-RNP) with higher prevalence of Raynaud phenomenon and photosensitivity; anti-deoxyribonucleoprotein (anti-DNP) with higher prevalence of arthritis and lower prevalence of renal disorder; anti-Scl-70 with higher prevalence of anemia and Raynaud phenomenon; anti-Jo-1 with higher prevalence of pericarditis; and anti-centromere with higher prevalence of Raynaud phenomenon. Three autoantibody clusters were identified: Cluster 1 (anti-Ro, anti-Sm, and anti-RNP [Ro/Sm/RNP], with a significantly lower percentage of elderly SLE and higher prevalence of photosensitivity, malar rash/discoid rash, Raynaud phenomenon, and leukopenia); Cluster 2 (anti-Ro [Ro], with a lower percentage of pediatric SLE); and Cluster 3 (the absence of anti-extractable nuclear antigen antibodies [ENA ve], with a lower percentage of adult SLE and lower prevalence of alopecia). In summary, this study not only confirms both anti-dsDNA and anti-Sm as specific markers for classifying SLE, but also demonstrates that photosensitivity is not associated with anti-Ro but with anti-RNP, and a negative association is found between renal disorder and anti-DNP in patients in South China. These results are different from results found in other populations. The higher prevalence of anti-dsDNA and renal disorder results in less difference in the prevalence of anti-dsDNA and renal disorder among the 3 autoantibody clusters in SLE patients in South China, which could be related to ethnicity and widespread industrial pollution in South China.
Topics: Adolescent; Adult; Autoantibodies; China; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Retrospective Studies; Risk Factors
PubMed: 20075706
DOI: 10.1097/MD.0b013e3181cb449c -
Cancer Epidemiology, Biomarkers &... Dec 2020In spite of the progress made in treatment and early diagnosis, breast cancer remains a major public health issue worldwide. Although modern image-based screening...
In spite of the progress made in treatment and early diagnosis, breast cancer remains a major public health issue worldwide. Although modern image-based screening modalities have significantly improved early diagnosis, around 15% to 20% of breast cancers still go undetected. In underdeveloped countries, lack of resources and cost concerns prevent implementing mammography for routine screening. Noninvasive, low-cost, blood-based markers for early breast cancer diagnosis would be an invaluable alternative that would complement mammography screening. Tumor-specific autoantibodies are excellent biosensors that could be exploited to monitor disease-specific changes years before disease onset. Although clinically informative autoantibody markers for early breast cancer screening have yet to emerge, progress has been made in the development of tools to discover and validate promising autoantibody signatures. This review focuses on the current progress toward the development of autoantibody-based early screening markers for breast cancer.
Topics: Autoantibodies; Breast Neoplasms; Early Detection of Cancer; Female; Humans
PubMed: 32994341
DOI: 10.1158/1055-9965.EPI-20-0331