Baylor Institute for Immunology Research

Panda, S. K., V. Facchinetti, E. Voynova, S. Hanabuchi, J. L. Karnell, R. N. Hanna, R. Kolbeck, M. A. Sanjuan, R. Ettinger and Y. J. Liu (2018). “Galectin-9 inhibits TLR7-mediated autoimmunity in murine lupus models.” J Clin Invest Apr 3. Epub ahead of print].

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Uncontrolled secretion of type I IFN, as the result of endosomal TLR (i.e., TLR7 and TLR9) signaling in plasmacytoid DCs (pDCs), and abnormal production of autoantibodies by B cells are critical for systemic lupus erythematosus (SLE) pathogenesis. The importance of galectin-9 (Gal-9) in regulating various autoimmune diseases, including lupus, has been demonstrated. However, the precise mechanism by which Gal-9 mediates this effect remains unclear. Here, using spontaneous murine models of lupus (i.e., BXSB/MpJ and NZB/W F1 mice), we demonstrate that administration of Gal-9 results in reduced TLR7-mediated autoimmune manifestations. While investigating the mechanism underlying this phenomenon, we observed that Gal-9 inhibits the phenotypic maturation of pDCs and B cells and abrogates their ability to mount cytokine responses to TLR7/TLR9 ligands. Importantly, immunocomplex-mediated (IC-mediated) and neutrophil extracellular trap-mediated (NET-mediated) pDC activation was inhibited by Gal-9. Additionally, the mTOR/p70S6K pathway, which is recruited by both pDCs and B cells for TLR-mediated IFN secretion and autoantibody generation, respectively, was attenuated. Gal-9 was found to exert its inhibitory effect on both the cells by interacting with CD44.

Ameen, R., S. A. Shemmari and M. Askar (2017). “Next-generation sequencing characterization of HLA in multi-generation families of Kuwaiti descent.” Hum Immunol.

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The frequency of HLA genes in one population may not accurately represent frequencies in other populations. In this study, we characterized extended human leukocyte antigen (HLA) haplotypes in several families of Kuwaiti descent by high-resolution typing using next-generation technology. A total 81 members (including patients and related donors) from 21 families were enrolled. No haplotypes were shared among multiple families. Of 77 haplotypes identified, 23 were not listed in the HaploStats database. Two haplotypes were most common in African Americans, six in Asian Pacific Islanders, three in Caucasians, three in Hispanics, and three in Native Americans. The remaining identified haplotypes were not among the most common 200 HLA haplotypes in any of the five major populations. This cohort had 202 (19%) unique alleles, including 20 rare alleles, 16 very rare alleles, and 2 novel ones. Furthermore, no frequency data were available for 30% (23/77) of the observed haplotypes, and 6% (3/49) of B approximately C blocks identified were not available in the HaploStats database. Kuwaiti individuals carry unique HLA haplotypes that are not shared by the majority of individuals historically reported to the US National Marrow Donor Program registry.

Frieder, J., D. Kivelevitch, C. T. Fiore, S. Saad and A. Menter (2017). “The impact of biologic agents on health-related quality of life outcomes in patients with psoriasis.” Expert Rev Clin Immunol: 1-19.

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INTRODUCTION: Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements. Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-alpha (TNF-alpha) and the interleukin (IL)-12/23 and IL-17 immune pathways. However, relatively limited data is available evaluating their full effect on quality of life outcomes. This review will discuss the most relevant and up-to-date clinical data on HRQoL measurements related to treatment with these aforementioned biologic agents. Expert commentary: Patient-reported outcomes (i.e. Dermatology Life Quality Index) are being used with increasing frequency in clinical trials, and provide valuable information on the impact of psoriasis on numerous aspects of day-to-day living. These outcomes must also be incorporated in clinical practice, in addition to physical assessment of disease severity, treatment decisions, and therapeutic response in the psoriasis patient population.

Wilder, E. G., J. Frieder, S. Sulhan, P. Michel, J. D. Cizenski, J. M. Wright and M. A. Menter (2017). “Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory conditions.” J Am Acad Dermatol 77(5): 809-830.

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The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologist must be aware. The second article in this continuing medical education series reviews inflammatory orocutaneous conditions and a number of genodermatoses. It is essential for dermatologists to be familiar with oral cavity manifestations associated with dermatologic diseases for prompt diagnosis, management, and appropriate referral to stomatology and dentistry.

Michel, P., A. Menter and J. Griffin (2017). “A congenital naevus in a blaschkoid distribution.” Clin Exp Dermatol: 2017 Oct [Epub ahead of print].

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NC is a rare hamartomatous proliferation of the pilo-sebaceous unit, usually evident at birth or appearingin early childhood. Most NCs arise sporadically, with afew adult onset cases reported secondary to trauma orirritation.1Men and women are equally affected, andthere is no evidence of racial aggregation. Rare associ-ations with cataracts, skeletal defects or central ner-vous system abnormalities characterize NC syndrome.