| First Author | Israel L | Year | 2017 |
| Journal | Cell | Volume | 168 |
| Issue | 5 | Pages | 789-800.e10 |
| PubMed ID | 28235196 | Mgi Jnum | J:263531 |
| Mgi Id | MGI:6162020 | Doi | 10.1016/j.cell.2017.01.039 |
| Citation | Israel L, et al. (2017) Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity. Cell 168(5):789-800.e10 |
| abstractText | The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient. |
