Phenotyping of Adaptive Immune Responses in Inflammatory Diseases

Humrich, Jens Y; Bernardes, Joana P.; Ludwig, Ralf J.; Klatzmann, David; Scheffold, Alexander

doi:10.3389/fimmu.2020.604464

Cited by 6 publications

(4 citation statements)

References 83 publications

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“…Biological treatments ( 93 ) and JAKi ( 96 ) hold significant promise as future therapeutic options. The lack of animal models underscores the importance of a comprehensive understanding of the pathogenesis of LP elucidating human phenotype-genotype correlations facilitating renewed efforts to unravel the cellular and molecular changes underlying the disease ( 219 ). Still, with the emergence of biological treatment options and of JAKi that both derived from careful clinical observations, the treatment landscape of LP will hopefully improve in the near future.…”

Section: Discussionmentioning

confidence: 99%

Lichen Planus

et al. 2021

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Lichen planus (LP) is a T cell-mediated disease affecting the stratified squamous epithelia of the skin and/or mucus membrane. Histologically, the disease is characterized by a lichenoid inflammatory infiltrate and vacuolar degeneration of the basal layer of the epidermis. LP has three major subtypes: Cutaneous, mucosal and appendageal LP. Rarely, it may affect the nails in the absence of skin and/or mucosal changes. LP may also be induced by several drugs, typically anti-hypertensive medication or be associated with infections, particularly viral hepatitis. The diagnosis is based on the clinical presentation and characteristic histological findings. Although the disease is often self-limiting, the intractable pruritus and painful mucosal erosions result in significant morbidity. The current first-line treatment are topical and/or systemic corticosteroids. In addition, immunosuppressants may be used as corticosteroid-sparing agents. These, however are often not sufficient to control disease. Janus kinase inhibitors and biologics (anti-IL-12/23, anti-IL17) have emerged as novel future treatment options. Thus, one may expect a dramatic change of the treatment landscape of LP in the near future.

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Section: Discussionmentioning

confidence: 99%

Lichen Planus

et al. 2021

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“…Despite some heterogeneity in the clinical responsiveness, which also arises from quite substantial variations in study design, applied treatment regimens and treatment duration, the results of most of these trials justify the further exploration of this novel therapeutic approach in autoimmune and rheumatic diseases and provide a valuable scientific basis for placebo-controlled and larger confirmatory clinical trials. The identification of molecular, cellular and epigenetic key events in response to low-dose IL-2 therapy at a common and disease-specific level, and of biomarkers which can predict the biological and clinical responsiveness to low-dose IL-2 therapy by advanced immunophenotyping technologies will allow to select appropriate diseases or patient subgroups and to stratify patients according to their individual immune signatures in the future ( 74 ). The clinical introduction of modified formulations of IL-2 with a longer half-life or increased selectivity for Treg could further contribute to a sustained clinical and biological efficacy, including stability of Treg lineage and function, and will ease its applicability for patients.…”

Section: Summary and Perspectivementioning

confidence: 99%

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

et al. 2021

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Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells. In addition, in some autoimmune diseases, a relative deficiency of IL-2 develops during disease pathogenesis leading to a disturbance of Treg homeostasis, which further amplifies the vicious cycle of tolerance breach and chronic inflammation. Low-dose IL-2 therapy aims either to compensate for this IL-2 deficiency to restore a physiological state or to strengthen the Treg population in order to be more effective in counter-regulating inflammation while avoiding global immunosuppression. Here we highlight key findings and summarize recent advances in the clinical translation of low-dose IL-2 therapy for the treatment of autoimmune and rheumatic diseases.

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“…Herein, they identified a higher frequency of a TIGIT+ CD4 T cell subset in autoantibody-positive, compared to autoantibody-negative first-degree relatives. This underscores the importance of immunophenotyping in patients and risk populations to unravel molecular pathways in autoimmune pre-diseases ( 24 ). Zotti et al.…”

Section: From Health To Autoimmunitymentioning

confidence: 93%

Editorial: Autoimmune pre-disease

et al. 2023

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According to the revised Witebsky postulates, diseases are of an autoimmune nature if, (i) the clinical phenotype can be reproduced through the transfer of autoantibodies and/or lymphocytes; (ii) the disease can be reproduced in experimental animal models; (iii) autoreactive T cells or autoantibodies are identified; and/or (iv) distinctive clinical observations, such as an HLA association, are found (1). These postulates mostly still hold true despite they were made 3 decades ago. However, in psoriasis, lichen sclerosus and lichen planus, which are considered chronic, non-communicable inflammatory diseases, autoreactive T cells and/or autoantibodies that potentially contribute to disease pathogenesis are also detected (2-5). Thus, rather than a clear distinction between autoimmune and chronic non-communicable inflammatory diseases, categorization of a given distinct disease may be better placed in the continuum between the two. Hence, within this research topic, we cover both "classic" autoimmune diseases, such as systemic lupus erythematosus (SLE), as well as non-communicable, inflammatory diseases with detectable autoimmunity, e.g., psoriasis.Autoimmune diseases develop over a long time, which at least spans over several years. This is maybe best demonstrated by the presence of disease-specific autoantibodies years prior to diagnosis of the corresponding autoimmune disease (6-10). The presence of disease-specific autoantibodies, does not, however, reliably predict if clinical manifestation of the corresponding autoimmune disease will occur in the future. Therefore, definite biomarkers that define the transition (i) from health to autoimmunity, (ii) from autoimmunity to autoimmune disease, and (iii) to chronicity or resolution of inflammation (Figure 1) would allow to implement measures to slow or prevent disease progression. This would have a significant impact on affected individuals, as well as the healthcare system because the incidence of autoimmune and non-communicable inflammatory diseases is rising and there are still many unmet medical needs in the care of patients with these diagnoses (12, 13).

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Phenotyping of Adaptive Immune Responses in Inflammatory Diseases

Cited by 6 publications

References 83 publications

Lichen Planus

Lichen Planus

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Editorial: Autoimmune pre-disease

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