Saburo Matsubara

Monocyte Chemotactic Factor in Rheumatoid Arthritis Synovial Tissue PROBABLY A CROSS-LINKED DERIVATIVE OF S19 RIBOSOMAL PROTEIN

The extracts of rheumatoid arthritis-synovial lesions from seven patients possessed a strong chemotactic activity for monocytes and a negligible one for polymorphonuclear leukocytes. These results are consistent with a prominent histological feature of the synovial lesion, the mononuclear cell predominant infiltration. The major monocyte chemotactic factor in the synovial tissue extracts was purified to a single protein peak in reverse phase high performance liquid chromatography with a C4 column. NH-terminal amino acid analysis of the initial 20 residues yielded a single sequence. Surprisingly, this sequence was completely identical to that of S19 ribosomal protein. The purified sample demonstrated two protein bands in SDS-polyacrylamide gel electrophoresis with apparent molecular masses of 34 and 68 kDa. These sizes were 2 and 4 times that of S19 ribosomal protein, suggesting that the chemotactic factor would be a dimer or tetramer of S19 ribosomal protein cross-linked by factor XIIIa. A recombinant human S19 ribosomal protein was prepared as a fusion protein with a maltose binding protein in Escherichia coli. After treatment with factor XIIIa, cross-linked recombinant S19 ribosomal protein exhibited the monocyte chemotactic activity, although the untreated recombinant protein did not.

Factor XIII-dependent generation of 5th complement component(C5)-derived monocyte chemotactic factor coinciding with plasma clotting.

Blood coagulation or plasma clotting caused generation of a monocyte chemotactic factor(s) in vitro. The chemotactic factor, of which the apparent molecular mass was 75 kDa, shared antigenicity with complement C5 and possessed the affinity to monocytes, but not to polymorphonuclear leukocytes. The generation of the chemotactic factor was hindered in the presence of a thiol enzyme inhibitor, p-chloromercuriphenyl sulfonic acid, at the concentration of 1 mmol/l, although the gelation of plasma was apparently completed. Furthermore, the generation of chemotactic factor was not observed when a plasma deficient in blood coagulation factor XIII, which is a precursor of a thiol enzyme, plasma transglutaminase, was used; and the activity normally appeared when the deficient plasma was reconstituted with purified factor XIII or with a tissue transglutaminase prior to clotting. When the human sera were injected into guinea pig skin, the serum derived from normal plasma or from the reconstituted factor XIII deficient one caused mononuclear cell infiltration, however, the serum from the deficient plasma without reconstitution infiltrated to a significantly smaller extent. These results indicated that the complement system was initiated somehow during the clotting process resulting in the generation of the C5-derived monocyte chemotactic factor in cooperation with factor XIIIa (activated factor XIII).

Combined treatment with cyclophosphamide and prednisolone is effective for secondary amyloidosis with SAA1γ/γ genotype in a patient with rheumatoid arthritis

Abstract A 41-year-old woman, who had been diagnosed with rheumatoid arthritis (RA), was admitted because of proteinuria, and rheumatoid and gastrointestinal symptoms just 1 year after onset. Renal biopsy revealed marked amyloid deposits of AA (amyloid A)-type. Genotyping of serum amyloid A (SAA) showed that she was homozygous for SAA1γ. Combined treatment with cyclophosphamide and prednisolone led to remission of both RA disease activity and proteinuria. Since the renal dysfunction arose from amyloidosis, arrested renal deterioration and a remission of proteinuria would result from a reduction of amyloid deposits. Therefore, early usage of immunosuppresive therapy such as a combined treatment with these two medicines would be useful against systemic amyloidosis secondary to RA, even if the patient has the risky SAA1γ/γ genotype.