Clinical Reviews in Allergy & Immunology

Epigenetics is the study of heritable, reversible gene expression patterns that do not originate from alterations in the DNA sequence. Epigenetic modifications influence gene expression patterns and include DNA methylation, histone modifications, and gene regulation via non-coding RNAs. While the study of epigenetics has been most broadly applied to neoplastic diseases, the role of the epigenome in a wide range of disease processes including autoimmune, allergic, and inflammatory processes is increasingly being recognized...

Mast cells originate from the CD34+ /CD117+ hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators...

Alopecia areata (AA) is characterized by common non-scarring alopecia due to autoimmune disorders. To date, the specific pathogenesis underlying AA remains unknown. Thus, AA treatment in the dermatological clinic is still a challenge. Numerous clinical observations and experimental studies have established that melanocytes may be the trigger point that causes hair follicles to be attacked by the immune system. A possible mechanism is that the impaired melanocytes, under oxidative stress, cannot be repaired in time and causes apoptosis...

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers)...

Eczema herpeticum (EH) is a viral skin infection caused by herpes simplex virus (HSV) superimposed on eczematous skin lesions in atopic dermatitis (AD). Though the pathogenesis of EH has yet to be fully elucidated, the fact that EH is relatively rare despite a majority of adults showing serologic evidence of HSV exposure points to a genetic component predisposing to the disease. A number of genetic variants have been isolated in EH which may help distinguish a subgroup of patients susceptible to developing the condition...

Chronic spontaneous urticaria (CSU) is characterized by recurring wheals that last 6 weeks or longer without an identifiable cause. The estimated point prevalence of CSU worldwide is 1%. Furthermore, it has a significant impact on quality of life in both adults and pediatric patients and their families. Although it is most often a self-limited disease, some patients have urticaria refractory to first-line treatment: second-generation H1 antihistamines. In these patients, the use of targeted monoclonal antibodies is necessary...

Several rheumatic diseases have a perplexing association with cancer. Unraveling this mysterious connection is likely to provide deeper understanding regarding mechanisms governing the onset of both autoimmunity and cancer immunity, in addition to providing clinicians much needed guidance around whom and when to screen for occult malignancy. Systemic sclerosis (scleroderma) and dermatomyositis are two diseases in which the association with internal malignancy is well-described and can be considered as models from which to gain important insights that likely have broader applicability...

Finkelstein-Seidlmayer vasculitis, also referred to as acute hemorrhagic edema of young children, is a rare small-vessel leukocytoclastic vasculitis. This condition is skin-limited, mainly affects infants up to 2 years of age and spontaneously remits. It has been suggested that an infection or a vaccine precede (by ≤ 14 days) this vasculitis. To better understand the interplay between infections or vaccines and Finkelstein-Seidlmayer vasculitis, we utilized the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID...

Thoracic involvement is one of the main determinants of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs), with different prevalence and manifestations according to the underlying disease. Interstitial lung disease (ILD) is the most common pulmonary complication, particularly in patients with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). Other thoracic manifestations include pulmonary arterial hypertension (PAH), mostly in patients with SSc, airway disease, mainly in RA, and pleural involvement, which is common in systemic lupus erythematosus and RA, but rare in other ARDs...

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease with female susceptibility. It is characterized by over-activation of the immune system and deposit of autoimmune complex in multiple organs. High heterogeneity, unpredictable disease course of SLE as well as the lack of specific and sensitive biomarkers posed diagnostic challenges to clinicians. Despite the complicated clinical presentation and pathogenesis of SLE, research regarding this disease has made many significant breakthroughs over the past decades...

Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5-9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90...

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters...

Dermatomyositis is a chronic inflammatory disease involving the skin and muscles. It most commonly occurs in adults with preponderance in females, but pediatric occurrence is also possible. The risk of malignancy in adult patients with dermatomyositis was reported to be 4.66-fold higher compared to that in the general population. A significantly increased risk of malignancy was reported within the first 12 months following the diagnosis of dermatomyositis (standardized incidence ratio equaled 17). One of the characteristic laboratory findings associated with dermatomyositis is the presence of circulating autoantibodies which are classified into two subgroups: myositis-specific and myositis-associated autoantibodies...

This review highlights the 30 plus years research progress since the discovery of autoantibody to Ro52/TRIM21 in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). After the initial expression cloning of the Ro52 cDNA, it has taken many years to the current understanding in the interesting biological function of Ro52 as an E3 ubiquitin ligase and its role in innate immune clearance of intracellular IgG-bound complex. Early observations show that anti-Ro52, mostly associated with anti-SS-A/Ro60 and/or anti-SS-B/La, is commonly found in SLE (40-70%), SjS (70-90%), neonatal lupus erythematosus (NLE, 75-90%), and subacute cutaneous lupus erythematosus (50-60%)...

Anti-mitochondrial antibodies (AMA) are directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes (PDC-E2) and are the typical biomarkers of primary biliary cholangitis (PBC), being present in 90-95% of patients, with increasing sensitivity at increasing titers. Albeit being highly specific for PBC diagnosis, AMA can be detected in less than 1% of healthy subjects, and thus the management subjects with no sign or symptom of liver disease is still a challenge and data concerning clinical risk of developing PBC in this subgroup of patients are controversial...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton's tyrosine kinase have effectively eliminated B cells...

Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued by the International Autoimmune Hepatitis Group. They also allow the distinction between type 1 AIH, characterized by positive anti-nuclear and/or anti-smooth muscle antibody, and type 2 AIH, characterized by positive anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. Anti-soluble liver antigen is the only AIH-specific autoantibody, and is found in 20-30% of both type 1 and type 2 AIH...

Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models...

Systemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus...

As the field of inborn errors of immunity expands, providers continually update and fine-tune their diagnostic approach and selection of testing modalities to increase diagnostic accuracy. Here, we first describe a mechanistic consideration of laboratory testing, highlighting both benefits and drawbacks of currently clinically available testing modalities. Next, we provide methods in evaluation of patients presenting with concern for inborn errors of immunity as defined by the International Union of Immunological Societies 2019 phenotypic categories: primary antibody deficiencies, cellular and humoral immune deficiency, disorders of the innate immune system, and syndrome-associated and primary immune regulation disorders (PIRDs)...