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Muhammad Haroon,1 Oliver FitzGerald,1 Robert Winchester2 1Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland; 2Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: The picture of elements comprising the genetic susceptibility to develop psoriatic arthritis, especially those involving human leukocyte antigen alleles, is emerging in much greater clarity because of improvements in the methods of psoriatic arthritis ascertainment and in the technology of genetic typing. This new knowledge suggests there is genetic heterogeneity in the psoriasis phenotype, and that there are several genetically and clinically different forms of psoriatic arthritis. These genetic studies on psoriatic arthritis further reinforce the relationship of psoriatic arthritis to the other spondyloarthritides, but also raise novel questions of whether the effect of certain susceptibility genes may differ among them. Considerable evidence indicates that the clinical features reflect a CD8 T lymphocyte-driven immune response is present that is characterized by clonal expansion and differentiation towards memory-effector phenotypes. With the aid of new classification criteria, the typical clinical features of psoriatic arthritis involving different joints, entheses, and their related compartments are being better defined as distinctive characteristics of psoriatic arthritis or of the spondyloarthritis group of disorders. In the evaluation of an individual with psoriatic arthritis, taking a patient-focused perspective is recommended, which has the potential to enhance their quality of life significantly. The choice of current and emerging therapeutic agents from an increasing realm of conventional and biologic agents is becoming much better rationalized and more firmly based on evidence from clinical trials. Keywords: psoriatic arthritis, genetic susceptibility, heterogeneity, classification, diagnostic criteria, treatment

The “Ia-like” antigens characteristically present on the membrane of B lymphocytes were shown to be absent in most terminally differentiated Ig-producing plasma cells. This was most evident in analyses of myeloma plasma cells that uniformly lacked the Ia-antigens. Also, in B lymphoid cell lines, the lymphoblasts were uniformly Ia-positive but the plasma cells were negative. In contrast, however, the majority of plasma cells produced after pokeweed mitogen stimulation remained positive. Plasma cells in tonsil and in the tissue of peripheral blood of patients with Waldenström's macroglobulinemia were also sometimes Ia-positive although the majority were negative. Studies of membrane IgM and IgD indicated a similar loss in some instances. However, the SIg and Ia antigens were not invariably associated. These results lead to the conclusion that Ia-antigens are differentiation antigens for B cells and are usually lost by the end stage cells in this series.

Antibodies to surface determinants of human lymphocytes, recognized both by cytotoxicity of fluorescent antibody analysis, were shown to be specifically enriched over the serum levels in cryoprecipitates from patients with systemic lupus erythematosus (SLE). The antilymphocyte antibody was shown to be cold reactive and was exclusively IgM. It was distinct from IgM anti-IgG, which was also variably concentrated in the cryoprecipitates. The question whether the antilymphocyte antibodies appear in the cryoprecipitates as complexes because of interaction with surface membrane antigens, or simply because of cold reactive properties, remains to be determined. The possible clinical relevance of the cryoprecipitation of these antibodies in systemic lupus erythematosus is discussed.

Gamma globulin complexes were demonstrable in certain joint fluids from patients with rheumatoid arthritis by analytic and density gradient centrifugation. They form a continuum of high molecular weight components ranging from 7S to 30S and were dissociable primarily to 7S γG globulin. The larger complexes were also detectable by precipitation reactions with C1q and with γM rheumatoid factor. This permitted the isolation and partial characterization of the complexes. Non-immunoglobulin constituents were not detectable. Evidence was obtained that 7S γG globulin rheumatoid factors represented an important constituent of the complexes.

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Summary Certain cases of chronic lymphocytic leukemia possess monoclonal bands in the serum. Idiotypic antibodies to the isolated IgM protein of one such case demonstrated that the leukemic lymphocytes carried the identical specificity on their lymphocytes. Both the lymphocyte IgM and the IgD possessed this same specificity. This was demonstrated best through the use of rhodamine-conjugated Fab fragments of IgM- and IgD-specific antisera which were both capped by the idiotypic antiserum.

A receptor for IgM was demonstrated on the surface of human B lymphocytes by using a rosette technique with ox erythrocytes coated with rabbit IgM antibody (EAM). Lymphocytes forming rosettes with EAM did not bind sheep red cells, had membrane Ia-like antigens and, in some instances, surface immunoglobulin. The specificity of EAM rosettes was confirmed by inhibition experiments with purified human Ig. IgM but not IgG molecules inhibited the rosette reaction. In addition, inhibition of EAM rosettes with IgM fragments showed that the receptor has affinity for a part of the molecule located in the Fc portion. By analogy with the receptors previously found on certain human T cells, receptors for IgM were not detected on freshly isolated B cells, but were expressed after overnight culture in IgM-free media. Studies on different human lymphoid tissues showed that IgM receptors are expressed on a limited percentage of both circulating and noncirculating B cells. In addition to normal B cells, the malignant B cells of a majority of cases of chronic lymphocytic leukemia expressed the receptors for IgM.

We have recently shown that engagement of the human monocytic Ag CD14 by murine mAb induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion. To determine whether CD14 plays a role in monocyte-T cell interactions, we tested the effect of anti-CD14 mAb on the proliferation of human T cells. Our results show that anti-CD14 mAb strongly inhibited T cell proliferation induced by Ag, anti-CD3 mAb, and mitogenic lectins. Inhibition by anti-CD14 mAb was epitope-dependent and required physical contact between monocytes and T cells. CD14 engagement did not affect IL-2R expression or IL-2 synthesis but induced a state of unresponsiveness that was not IL-2 specific; proliferation of anti-CD3-activated T cell blasts in response to both IL-2 and IL-4 was abrogated by addition of monocytes preincubated with anti-CD14 mAb. Inhibition of T cell proliferation after engagement of CD14 on monocytes was likely to result from delivery of a negative signal to T cells, rather than from disruption of a costimulatory monocyte-derived signal, because incubation of monocytes with anti-CD14 mAb also inhibited monocyte-independent T cell proliferation induced by PMA and ionophore. These results, together, point to a role of CD14 in the monocyte-dependent regulation of T cell proliferation.

Brief digestion of human peripheral blood lymphocytes by vibrio cholera neuraminidase (VCN) revealed hidden components of the membrane. Autologous human serums contained antibodies directed to these components that were readily demonstrated by immunofluorescence. Antibodies of similar specificity were found in all normal serums. The antibodies were principally of the IgM variety with lesser amounts of the IgG class present. They were equally active at 4°C and 37°C. The VCN revealed membrane determinants were present in normal B and T lymphocytes, monocytes, lymphocytes of patients with chronic lymphatic leukemia and cells of lymphoid lines. The newly revealed determinants slowly disappeared upon culture of the lymphocytes. These hidden components were similarly demonstrated in erythrocyte membranes and represent the T antigen long known for the red blood cells. Absorption by either VCN treated autologous lymphocytes or erythrocytes removed all of the antibodies capable of reacting with both cell types. Absorption by VCN digested isologous lymphocytes removed all reactivity with autologous lymphocytes.

Direct immunofluorescence performed with the F(ab′)2 fragment of rabbit antibodies to IgG revealed that membrane bound IgG was only rarely found on the surface of small peripheral blood lymphocytes (PBL). In contrast whole antibodies to IgG used in fluorescence gave much higher levels of cells with IgG surface staining. This staining resulted from secondary IgG binding, in part due to the uptake of newly formed immune complexes. IgM-and IgD-bearing cells were brightly stained in relatively similar percentages by both the whole and F(ab′)2 forms of the class-specific antibodies; they constitute the principal membrane Ig of PBL. Evidence was obtained indicating that a special population of cells with Fc receptors but lacking membrane Ig was primarily involved in the high IgG binding. This population also formed sheep erythrocyte rosettes when optimal conditions were utilized.

Six monoclonal antibodies (MAb) which react with myelomonocytic cells representing various stages of differentiation, and which precipitate six different cell surface molecules, were identified. A 50 to 55 kilodalton (Kd) glycoprotein, restricted in expression to mature cells of the monocyte lineage, was detected by immunoprecipitation with antibody MoS39. By using COS-7 cells transfected with a cDNA clone encoding the MoS39 antigen, various well-described anti-monocyte MAb, including Mo2, My4, Leu-M3 (MoP9), MoP15, MoS1, and 63D3, also bound to MoS39-expressing COS-7 cells, suggesting that this group of antibodies reacted with the same glycoprotein. Immature cells of the myelomonocytic lineage were shown to express two distinct molecules: one with an m.w. of 26 to 28 Kd identified by antibody SG133, and the second, a 130 to 140 Kd glycoprotein identified by MoU26. Mature granulocytes were found to express a 60 Kd molecule identified by antibody SG185 which was absent from other cells of this lineage. Two other molecules were shown to be present on both mature and immature cells of the granulocytic and monocytic lineages: a 130 to 140 Kd glycoprotein identified by antibody SG134, and a 160 to 170 Kd glycoprotein recognized by antibody MoU48.