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Innate instruction of adaptive immunity was proposed more than 20 years ago as a mechanism by which long-lived lymphocyte responses are targeted to appropriate antigens. At the time Charles Janeway proposed this theory, most of the innate immune receptors were unknown and the pivotal role of the dendritic cell in instructing T cell priming was debated. There is now overwhelming evidence that the innate and adaptive branches of the immune system must interact to generate immunity. Much of this work has focused on families of innate immune receptors called pattern recognition receptors (PRRs) on dendritic cells, which translate these inflammatory triggers into productive T cell responses. Nevertheless, we are only beginning to understand how these defense molecules shape the generation of immunity. We review the varied roles of one class of PRRs, the NOD-like receptors (NLRs), in immune responses and propose a new model in which adaptive immunity requires coordinated PRR activation within the dendritic cell.

Medium-chain acyl-CoA dehydrogenase (MCAD; acyl-CoA:(acceptor) 2,3-oxidoreductase, EC 1.3.99.3) is one of three similar enzymes that catalyze the initial step of fatty acid fl-oxidation. Definition of the primary structure of MCAD and the tissue distribution of its mRNA is of biochemical and clinical importance because of the recent recognition of inherited MCAD deficiency in humans. The MCAD mRNA nucleotide sequence was determined from two overlapping cDNA clones isolated from human liver and placental cDNA libraries, respectively. The MCAD mRNA includes a 1263-base-pair coding region and a 738-base-pair 3'-nontranslated region. A partial amino acid sequence (137 residues) determined on peptides derived from MCAD purified from porcine liver confirmed the identity of the cDNA clone.Comparison of the amino acid sequence predicted from the human MCAD cDNA with the partial protein sequence of the porcine MCAD revealed a high degree (88%) of interspecies sequence identity. RNA blot analysis shows that MCAD mRNA is expressed in a variety of rat (2.2 kilobases) and human (2.4 kilobases) tissues. Blot hybridization of RNA prepared from cultured skin fibroblasts from a patient with MCAD deficiency disclosed that mRNA was present and of similar size to MCAD mRNA derived from control fibroblasts. The isolation and characterization of MCAD cDNA is an important step in the definition of the defect underlying MCAD deficiency and in understanding its metabolic consequences.

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BackgroundImmunogenicity due to antidrug antibodies (ADA) to tumor necrosis factor (TNF)-α antagonists is known to decrease treatment response. However, few studies have investigated ADA in ustekinumab, an interleukin-12 and -23 antagonist, in a clinical setting. This study aimed to investigate the immunogenicity of ustekinumab and its clinical consequences in psoriasis.MethodsThis prospective observational study enrolled 76 patients with plaque psoriasis who were treated with ustekinumab for a minimum of 7 months. Blood samples were drawn just prior to scheduled ustekinumab injection during clinic visits. Levels of anti-ustekinumab antibody (AUA) and serum ustekinumab concentration were measured respectively by radioimmunoassays and enzyme-linked immunoassays respectively, and correlated to clinical data and Psoriasis Area and Severity Index (PASI).ResultsAUA was detected in 6.5% of patients after a mean of 13 months of treatment. Patients with positive AUA had significantly lower serum ustekinumab concentrations (0.01 vs. 0.2 mg/L, p<0.001) and lower PASI 50 response than patients without AUA (0% vs. 69%, p = 0.004).The percentage of AUA formation was comparable between patients who had failed previous adalimumab with or without anti-adalimumab antibodies (AAA) (14.3% vs. 12.5%, p = 1.00). However, a higher proportion of switchers without AAA obtaining PASI50 (71.4% vs. 37.5%) and PASI75 response (42.9% vs.12.5%) within 7 months of ustekinumab treatment than with AAA though this difference did not reach statistical significance.ConclusionsOur results suggest that presence of AUA was significantly associated with treatment failure for ustekinumab, though limited by a small sample size. Also, determining the presence of ADA to antecedent TNF-α antagonists may assist in choosing an optimized subsequent treatment modality achieving treatment success.

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Background: Fox-Fordyce (FFD), also known as apocrine military, is an uncommon chronic inflammation of the apocrine sweat glands. It is characterized by pruritic, papular eruptions in apocrine-gland-bearing regions. FFD was described a century ago, but the exact pathogenesis of the disease and the management are not well understood. Aims:This paper provides a wide understanding of the pathophysiology, clinical findings, and management of Fox-Fordyce disease. Its aim is to help the physician to diagnose and manage this entity accordingly.Methods: A research was done using PubMed database on 12 April 12, 2020, and in order to retrieve all case reports, case series, cohort studies, randomized, and nonrandomized clinical trials were included describing FFD among patients.Results: A total of 43 articles and 68 patients were included in the study. The majority of patients were young females. The disease was bilateral in 90%, affected the axillae and to a lesser extent the pubic and the periareolar areas and rarely the thoracic area, the abdominal area, and the face. FFD followed a relapsing and remitting course, and an evident improvement in disease course was noted after menopause. Conclusion:The typical FFD patient is a post-pubertal female and pre-menopause, presenting with pruritic papules in apocrine-gland-bearing regions. FFD can be sporadic or occurs in family, and it can be asymptomatic in 1/(3-4) of patients and can be triggered by laser hair removal and hormonal changes. Further randomized clinical trials assessing different treatment of FFD are now warranted.