Accumulation of VH Replacement Products in IgH Genes Derived from Autoimmune Diseases and Anti-Viral Responses in Human

Protein kinase Cθ (PKCθ) is a member of a large family of serine/threonine kinases that are involved in diverse cellular functions. PKCθ has roles in T-cell activation and survival, where the dependency of T-cell responses on this enzyme appears to be dictated by both the nature of the antigen and by the inflammatory environment. Studies in PKCθ-deficient mice have demonstrated that although anti-viral responses are PKCθ-independent, T-cell responses associated with autoimmune diseases are PKCθ-dependent. PKCθ-deficient mice are either resistant to or show markedly reduced symptoms in models of MS (multiple sclerosis), IBD (inflammatory bowel disease), arthritis and asthma. Thus potent and selective inhibition of PKCθ has the potential to block T-cell-mediated autoimmunity without compromising anti-viral responses. The present review describes the design and optimization of potent and selective PKCθ inhibitors and their efficacy in both in vitro and in vivo studies. First, our compounds confirm the critical role for PKCθ in T-cell activation and proliferation and secondly they help to demonstrate that murine and human memory T-cell function continues to be dependent on this enzyme. In addition, these inhibitors demonstrate impressive efficacy in treating established autoimmune disease in murine models of IBD and MS.

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Laryngeal Manifestations of Autoimmune Diseases

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2020_persp-19-00168 ◽

2020 ◽

Vol 5 (2) ◽

pp. 439-456

Author(s):

Jenny L. Pierce

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Patient Outcomes ◽

Correct Diagnosis ◽

Upper Airway ◽

Clinical Implications ◽

Laryngeal Function ◽

The Past ◽

Referral Practices ◽

Timely Referral

Purpose This review article provides an overview of autoimmune diseases and their effects on voice and laryngeal function. Method A literature review was conducted in PubMed. Combinations of the following keywords were used: “autoimmune disease and upper airway,” “larynx,” “cough,” “voice,” “dysphonia,” and “dyspnea.” Precedence was given to articles published in the past 10 years due to recent advances in this area and to review articles. Ultimately, 115 articles were included for review. Results Approximately 81 autoimmune diseases exist, with 18 of those highlighted in the literature as having laryngeal involvement. The general and laryngeal manifestations of these 18 are discussed in detail, in addition to the clinical implications for a laryngeal expert. Conclusions Voice, breathing, and cough symptoms may be an indication of underlying autoimmune disease. However, these symptoms are often similar to those in the general population. Appropriate differential diagnosis and timely referral practices maximize patient outcomes. Guidelines are provided to facilitate correct diagnosis when an autoimmune disease is suspected.

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