High titers of anti-GPI antibodies are present in arthritis-resistant C57BL/6 mice (H-2b) [ 11, 12], although the T cells of these animals exhibited weak GPI responses compared with arthritis-susceptible DBA/1 mice (H-2q).
By tracking the anti-GPI B cell response in different anatomic sites at different stages of the disease (preclinical, acute, and chronic), the authors could demonstrate, in parallel with arthritis onset and appearance of serum autoantibodies, the localization of anti-GPI+ B cells (and differentiation of anti-GPI secreting B cells) within GCs and medullary cords of peripheral reactive LNs.
The autoimmune target for the KRN T-cell and antibody response is GPI, which is involved in glycolysis and is ubiquitously present within the cytosol and within tissue at low levels.
These findings highlight autoimmune responses to GPI are occurring in some patients with RA, and GPI can be a target of antigen-specific therapies to them - although further studies are needed to clarify the exact pathological role of GPI in RA.
A recent report also revealed that CD36-deficient mice showed impaired tumor necrosis factor-alpha (TNF-α) secretion in response to glycosylphosphatidylinositol (GPI) from P. falciparum and higher parasitemia levels and mortality when infected with Plasmodium chabaudi chabaudi AS (P. chabaudi chabaudi AS) [18].
In our experience, the apomorphine response in the GPi of human PD patients was characterized by a dose-dependent fast inhibition and showed partial desensitization.
In addition, the group pTPA.GPI-PA63 also displayed low magnitude MHC-II restricted (CD1d-independent) NKT cell and CD4+ T cell helper responses in response to non-GPI attached PA63 peptides which overall resulted in the heightened responses seen for this group.
Mice lacking both TLR2 and TLR4, but not TLR2 alone, had completely abrogated production of TNF in the response of T. gondii GPI [ 24].
The GPI transamidase recognizes a C-terminal GPI-anchor signal peptide (GPI-SP), which is cleaved concomitantly to the attachment of the GPI-anchor.
Although the interaction of TLR4 with P. Falciparum is not fully understood, Krishnegowda and colleagues showed in vitro that TLR4 can be activated by malarial glycosylphosphatidylinositols (GPIs) to induce a pro-inflammatory response.
In this regard, we demonstrated a clear therapeutic effect for TNF antagonist in mice with GPI-induced arthritis, and the therapeutic response correlated with the in vitro regulation of TNF production.
