Predictive modeling of human disease based on the microbiota holds great potential yet remains challenging. Here, 50 adults underwent controlled transitions from naturally occurring gingivitis, to healthy gingivae (baseline), and to experimental gingivitis (EG). In diseased plaque microbiota, 27 bacterial genera changed in relative abundance and functional genes including 33 flagellar biosynthesis-related groups were enriched. Plaque microbiota structure exhibited a continuous gradient along the first principal component, reflecting transition from healthy to diseased states, which correlated with Mazza Gingival Index. We identified two host types with distinct gingivitis sensitivity. Our proposed microbial indices of gingivitis classified host types with 74% reliability, and, when tested on another 41-member cohort, distinguished healthy from diseased individuals with 95% accuracy. Furthermore, the state of the microbiota in naturally occurring gingivitis predicted the microbiota state and severity of subsequent EG (but not the state of the microbiota during the healthy baseline period). Because the effect of disease is greater than interpersonal variation in plaque, in contrast to the gut, plaque microbiota may provide advantages in predictive modeling of oral diseases.

We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

Systemic mastocytosis (SM) is characterized by infiltration of neoplastic mast cells in one or more organ systems. SM in association with plasma cell dyscrasia is very rare. We report a first case of indolent SM (ISM) associated with light chain deposition disease (LCDD) in a kidney biopsy from a 59-year-old female presenting with skin rash, elevated serum creatinine, hematuria and mild proteinuria. Subsequent workup demonstrated IgG kappa monoclonal protein in serum and urine. A bone marrow biopsy revealed neoplastic mast cells involving bone marrow without evidence of clonal myeloid or lymphoid proliferation. Kidney biopsy demonstrated modest mesangial expansion detected by light microscopy and unequivocal evidence of monoclonal kappa light chain deposition within glomerular capillaries, tubular basement membranes and vascular walls detected by immunofluorescence and/or electron microscopy, along with equivocal evidence of light chain cast nephropathy. Despite treatment with bortezomib and dexamethasone, her renal function was progressively declined over the next 6 months. This case is a reminder that SM can coincide with LCDD, which requires clinical suspicion and multimodality workup on a kidney biopsy including immunofluorescence and electron microscopy to reach the correct diagnosis.

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