Rheumatoid factors monoclonal

Crouzier, R., T. Martin, and J. L. Pasquali. 1995. Heavy chain variable region, light chain variable region, and heavy chain CDR3 influences on the mono- and polyreactivity and on the affinity of human monoclonal rheumatoid factors. J. Immunol. 154 4526-4535. 

Monoclonal rheumatoid factor assay, Clq binding and deviation tests, complement consumption tests... 

Fig. 4. Detection of immune complexes in supemates from a precipitin curve. Lower panel total protein precipitated by increasing amounts of keyhole limpet hemocyanin (KLH) added to a human anti-KLH serum. Upper panel supemates were analyzed for immune complexes by the conglutinin ( ), monoclonal rheumatoid factor (A), Raji ( ), and staphylococci binding (B) assay, and results expressed as pg/ml aggregated IgG equivalents per ml. Clq binding assay (O) results are expressed as percent Clq precipitated. (Reproduced with permission, J. S. McDougal, M. Hubbard, P. I. Strobel, and F. C. McDuffie, J. Lab. Clin. Med. 100, 705-719, 1982.)...

Gl. Gabriel, A., and Agnello, V., Detection of immune complexes The use of radioimmunoassays with Clq and monoclonal rheumatoid factor. J. Clin. Invest. 59, 990-1001 (1977). 

W23. Winchester, R. M., Kunkel, H. G., and Agnello, V., Occurrence of 7-globulin complexes in serum and joint fluid of rheumatoid arthritis patients Use of monoclonal rheumatoid factors as reagents for their demonstration. J. Exp. Med. 134, 286s-295s (1971). 

For discussions of monoclonal rheumatoid factors, cryoglobulins, and cold agglutinins, see Chapter 11. 

There exist both heterogeneous and monoclonal rheumatoid factors. Most patients with rheumatoid arthritis possess heterogeneous antiglobulins, although monoclonal factors sometimes appear after prolonged illness. A substantial number of monoclonal proteins with anti-IgG activity have, however, been found in the sera of patients with... 

A general discussion of rheumatoid factors was presented in Chapter 3. In this section we will consider monoclonal rheumatoid factors which occur in about 1% of patients with rheumatoid arthritis (50). In 1971, Potter (51) cited 24 such cases in the literature and numerous additional examples have been reported since then. Many more have undoubtedly been unreported, particularly as special conditions, such as low pH, are sometimes necessary to demonstrate RF activity in monoclonal proteins. 

Secondary paraproteinemias may be seen in association with hematopoietic cancers (e.g., lymphomas and leukemias), other neoplasms (e.g., colon carcinoma), long-standing chronic urinary or biliary tract infection, rheumatoid factor related to IgM monoclonal protein, and amyloidosis. 

Williams R C Jr, Malone C C (1992). Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid factors react with epitopes induced in Gm(a), Gm(g-) IgG by interaction with antigen or by nonspecific aggregation. A possible mechanism for the in vivo generation of rheumatoid factors. J. Immunol. 149 1817-1824. 

A major difference between a monoclonal anti-IgG and polyclonal rheumatoid factor is that the former would be expected to recognize only one kind of antigenic determinant on the IgG molecule. Stone and... 

Although monoclonal anti-IgG appears to be monospecific, anti-IgG from different patients may have different specificities. This is shown, for example, by differences in their relative strengths of interaction with human, as compared to rabbit IgG. The ratios of the two titers vary from one anti-IgG to the next and an occasional monoclonal IgM protein reacts more strongly with rabbit than with human IgG (58). Anti-IgG from one individual reacted with human IgG only after treatment of the latter with neuraminidase to remove sialic acid (59). We have not found a report of a monoclonal IgM reactive with a Gm faetor on IgG, although there are, of course, numerous instances of polyclonal rheumatoid factors with such reactivity. 

We have used a series of IgG preparations differing in their content of oligosaccharide chains lacking galactose by 18-86% to determine whether changes in sugar content affect the binding of rheumatoid factor [40]. Five of 16 monoclonal... 

Soltys AJ, Hay FC, Bond A, Axford JS, Jones MG, Randen I, Thompson K Natvig J. The binding of synovial tissue-derived human monoclonal immunoglobulin M rheumatoid factor to immunoglobulin G preparations of differing galactose content. Scan J Immunol (1994) 40(2) 135-143. 

Tumor Necrosis Factor There are two types of tumor necrosis factor TNF-a and TNF- 8. Of the two, TNF-a has been studied in more detail. TNF-a is a 157 amino acid polypeptide. It is a mediator of immune regulation, including the activation of macrophages and induction of the proliferation of T cells. Another TNF-a function is its cytotoxic effects on a number of tumor cells. Recent research, however, concentrates on its property in the stimulation of inflammation, particularly in the case of rheumatoid arthritis. Clinical trials are being conducted with drugs to block TNF-a with anti-TNF-a monoclonal antibodies. These antibodies target the excessive levels of TNF-a in the synovial fluid of joints and provide relief to sufferers of rheumatoid arthritis (Exhibit 4.10). 

Maini, R. N., Breedveld, E. C., Kalden, J. R., et al. (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis and Rheumatism. 41, 1552-1563. 

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

Barrera, P., Joosten, L. A., den Broeder, A. A., van de Putte, L. B., van Riel, P. L., and van den Berg, W. B. (2001) Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 60, 660-669. 

Adalimumab is a recombinant, fully human antitumor necrosis factor monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis. It has to be injected subcutaneously. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. Rare side effects include worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis like neurological disease. 

Mecfianism of Action A monoclonal antibody that binds specifically to tumor necrosis factor (TNF) alpha, blocking its interaction with cell surface TNF receptors, Tfier-apeutic Effect Reduces inflammation, tenderness, and swelling of joints slows or prevents progressive destruction of joints in rheumatoid arthritis. 

Some drugs situations are frankly confusing and need to be explored in greater depth. For example, tumor necrosis factor (TNF) is produced in the body as a natural defense against the many spontaneous tumors that arise in the body and has been suggested as a treatment for cancer, which may very well be effective under some conditions. However, TNF is also believed to be involved in the pain associated with rheumatoid arthritis, and monoclonal antibodies with specific activity against TNF are now on the market. The use of TNF is therefore a complex issue and needs to be evaluated with considerable care. 

Maini, R., St. Clair, E. W., Breedveld, F., Furst, D., Kalden, J., Weisman, M., Smolen, J., Emery, P. 1999. Infliximab (chimeric anti-tumor necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate a randomised phase HI trial. Attract study group. Lancet 354 1932-1939. 

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