Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss.

Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of ß2 integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)-deficient mice--which exhibit the LAD-I periodontal phenotype--was associated with excessive production of predominantly T cell-derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17-targeted therapy for periodontitis in LAD-I patients.

Oral manifestations of systemic autoimmune and inflammatory diseases: diagnosis and clinical management.

CONTEXT: Systemic autoimmune and inflammatory diseases often manifest oral lesions in their earliest stages, and early diagnosis, which may be spurred by a dental examination, is key for improved outcomes. After systemic diagnosis, oral lesions benefit from specialized care by dentists in collaboration with the medical team. This review aims to educate dental clinicians about the most relevant systemic autoimmune and inflammatory conditions with accompanying oral lesions, their implications for health, and management strategies supported by the biomedical literature and clinical experience. Ulcerative conditions including Behcet and Crohn diseases are discussed, along with rheumatic conditions including Sjögren syndrome, lupus erythematosus, and rheumatoid arthritis. EVIDENCE ACQUISITION: Evidence was accumulated through PubMed searches using pertinent keywords for each subsection. References were reviewed and original publications examined to verify the accuracy of the information. We focused on evidence included in current reviews and randomized trials. Recommendations were supported by multiple studies and consensus expert opinion. EVIDENCE SYNTHESIS: Disease phenotypes described and clinical recommendations were synthesized from best-quality evidence available for each disease. Efforts were made to describe evidence selection within each disease section. CONCLUSIONS: Dentists play an important role in the early detection and multidisciplinary medical management of complex autoimmune diseases. It is important to recognize prevalent medical and dental issues and special needs of patients with autoimmune conditions. The management of many inflammatory conditions is similar, and often begins with the use of topical steroids, analgesics, and antimicrobial treatments, in addition to careful attention to oral hygiene and appropriate fluoride usage. In this brief review, we aim to discuss the presentation/prevalence, diagnosis, and treatment of oral manifestations encountered in autoimmune, autoinflammatory and systemic chronic inflammatory diseases. Systemic autoimmune conditions are estimated to affect 5% to 8% of Americans.(1) Oral manifestations are encountered with high frequency, and are often the first clinical signs or symptoms of the general disease. Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. The dental practitioner may be asked to play a primary role in the diagnosis of such conditions and to participate with other health professionals working together to achieve effective clinical management. To aid in this process, we discuss in this article the current general knowledge of systemic autoimmune conditions that present with prevalent oral manifestations. The focus is on the diagnosis and management of the oral component of each disease. Importantly, whereas the etiology and pathogenesis and systemic clinical presentation may vary, presentation in the oral cavity is often similar and many conditions involve oral ulcerations. For this reason, we discuss the differential diagnosis and management of the most common oral ulcerations in a general section and subsequently address individual conditions that present with oral ulcerations. Similarly, treatment of various autoimmune/inflammatory oral conditions is often common and involves modulation or suppression of the immune response locally and/or systemically and will be therefore addressed in a common section as well as individually for each disease when unique treatment regimens are recommended. We present here our general treatment recommendations based on clinical experience and literature review; however, it is critical that good clinical judgment and specifics of an individual case should determine the appropriate dental/oral medicine intervention for a specific patient.

Refractory major aphthous stomatitis managed with systemic immunosuppressants: a case report.

This article presents an unusual case of major recurrent aphthous stomatitis that was refractory to multiple topical and systemic immunosuppressive therapies. Ultimately, thalidomide was selected despite its well-recognized adverse potential, and was successful in producing remission of ulcers. Strict clinical protocols were followed for this therapy in collaboration with numerous medical providers. This case illustrates the ability of multiple oral health and medical providers to collaborate in the diagnosis, management, and follow-up of a patient with an oral vesiculoerosive disease.

Effects of pH on human bone marrow stromal cells in vitro: implications for tissue engineering of bone.

The objective of this study was to address the hypothesis that changes in extracellular pH alter collagen gene expression, collagen synthesis, and alkaline phosphatase activity in bone marrow stromal cells (BMSCs). Potential effects of pH on cell function are of particular importance for tissue engineering because considerable effort is being placed on engineering biodegradable polymers that may generate a local acidic microenvironment on degradation. Human and murine single-cell marrow suspensions were plated at a density of 2 x 10(4) cells/cm(2). After 7 days in culture, the pH of the culture medium was adjusted to one of six ranges: > or = 7.8, 7.5.-7.7, 7.2-7.4, 6.9-7.1, 6.6-6.8, or < or = 6.5. After 48 h of exposure to an altered pH, alkaline phosphatase activity and collagen synthesis decreased significantly with decreasing pH. This decrease was two-to threefold as pH decreased from 7.5 to 6.6. In contrast, alpha1(I) procollagen mRNA levels increased two- to threefold as pH was decreased. The trend in osteocalcin mRNA expression was opposite to that of collagen. Small shifts in extracellular pH led to significant changes in the ability of BMSCs to express markers of the osteoblast phenotype. These pH effects potentially relate to the microenvironment supplied by a tissue-engineering scaffold and suggest that degrading polymer scaffolds may influence the biologic activity of the cells in the immediate environment.