scholarly journals Human rheumatoid factor cross-idiotypes. IV. Studies on WA XId-positive IgM without rheumatoid factor activity provide evidence that the WA XId is not unique to rheumatoid factors and is distinct from the 17.109 and G6 XIds.

1993 ◽  
Vol 178 (6) ◽  
pp. 1903-1911 ◽  
Author(s):  
G B Knight ◽  
V Agnello ◽  
V Bonagura ◽  
J L Barnes ◽  
D J Panka ◽  
...  
Keyword(s):  
Rheumatoid Factor ◽  
Mixed Cryoglobulinemia ◽  
Structural Features ◽  
Peripheral Blood Lymphocytes ◽  
Pokeweed Mitogen ◽  
Rheumatoid Factors ◽  
Antigen Specificity ◽  
Sequence Comparisons ◽  
Normal Individuals ◽  
Somatic Diversification

The WA cross-idiotype (XId) is the major XId among human monoclonal rheumatoid factors (mRF) and is almost always associated with the light (L) chain XId, 17.109, and the heavy (H) chain XId, G6. A cell line, 35G6, was cloned that bears the WA XId, but shows no reactivity with immunoglobulin G (IgG) and is negative for the 17.109 and G6 XIds. The 35G6 L chain appears to be derived from the same VKIII-JKI genes as most WA mRFs L chains. In contrast to the WA mRFs H chains in which VH1 genes are used, the 35G6 IgM expresses a VH3 gene. Sequence comparisons with other WA XId-positive mRF suggested several common structural features that may be related to the WA XId and differences that may relate to lack of IgG reactivity. Cells similar to 35G6 have previously been described in pokeweed mitogen-stimulated cell lines of peripheral blood lymphocytes from normal individuals and patients with rheumatoid arthritis and type II mixed cryoglobulinemia. These observations were confirmed, and in addition, it was shown that the majority of WA XId-positive cells in these cultures were negative for the 17.109 and G6 XIds. The presence of the WA XId in the absence of IgG reactivity suggests that the WA XId is more directly associated with an antigen specificity other than IgG, and its association with RF activity may be incidental. It is postulated that these WA XId-positive RF-negative antibodies may serve a physiologic role as natural antibodies to a pervasive pathogen, and that IgG reactivity is a consequence of somatic diversification accompanying proliferation of the WA XId-positive RF-negative cell.

scholarly journals The majority of peripheral blood monoclonal IgM secreting cells are CD5 negative in three patients with mixed cryoglobulinemia

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1761-1765
Author(s):  
JL Pasquali ◽  
C Waltzinger ◽  
JL Kuntz ◽  
AM Knapp ◽  
H Levallois
Keyword(s):  
B Cell ◽  
Rheumatoid Factor ◽  
Peripheral Blood ◽  
Mixed Cryoglobulinemia ◽  
Lymphocytic Leukemia ◽  
Rheumatoid Factors ◽  
Membrane Expression ◽  
Variable Regions ◽  
Membrane Bound ◽  
Human B Cell

The mixed cryoglobulinemia is considered to be a nonmalignant human B- cell proliferation that frequently produces a monoclonal IgM with anti- IgG activity (rheumatoid factor). Using murine monoclonal anti- idiotypic antibodies specific for private or minor idiotopes on monoclonal IgM from three patients suffering from nonmalignant mixed cryoglobulinemia, we investigated the presence of the CD5 antigen on the monoclonal IgM producing cells in these patients. It is shown by two-color cytofluorometric analysis that the majority of the peripheral blood monoclonal IgM rheumatoid factor secreting cells is CD5 negative in these three patients. One of the monoclonal rheumatoid factor K variable regions was sequenced at the protein level and belongs to the human VK III group, as a high proportion of monoclonal rheumatoid factors and some B-cell chronic lymphocytic leukemia (CLL) membrane bound Igs. Thus, despite the preferential use of similar VK genes and the absence of somatic mutation affecting these variable regions in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferating B cells differ in the CD5 membrane expression.

scholarly journals The majority of peripheral blood monoclonal IgM secreting cells are CD5 negative in three patients with mixed cryoglobulinemia

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1761-1765 ◽  
Author(s):  
JL Pasquali ◽  
C Waltzinger ◽  
JL Kuntz ◽  
AM Knapp ◽  
H Levallois
Keyword(s):  
B Cell ◽  
Rheumatoid Factor ◽  
Peripheral Blood ◽  
Mixed Cryoglobulinemia ◽  
Lymphocytic Leukemia ◽  
Rheumatoid Factors ◽  
Membrane Expression ◽  
Variable Regions ◽  
Membrane Bound ◽  
Human B Cell

Abstract The mixed cryoglobulinemia is considered to be a nonmalignant human B- cell proliferation that frequently produces a monoclonal IgM with anti- IgG activity (rheumatoid factor). Using murine monoclonal anti- idiotypic antibodies specific for private or minor idiotopes on monoclonal IgM from three patients suffering from nonmalignant mixed cryoglobulinemia, we investigated the presence of the CD5 antigen on the monoclonal IgM producing cells in these patients. It is shown by two-color cytofluorometric analysis that the majority of the peripheral blood monoclonal IgM rheumatoid factor secreting cells is CD5 negative in these three patients. One of the monoclonal rheumatoid factor K variable regions was sequenced at the protein level and belongs to the human VK III group, as a high proportion of monoclonal rheumatoid factors and some B-cell chronic lymphocytic leukemia (CLL) membrane bound Igs. Thus, despite the preferential use of similar VK genes and the absence of somatic mutation affecting these variable regions in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferating B cells differ in the CD5 membrane expression.

scholarly journals Human rheumatoid factor crossidiotypes. I. WA and BLA are heat-labile conformational antigens requiring both heavy and light chains.

1986 ◽  
Vol 164 (5) ◽  
pp. 1809-1814 ◽  
Author(s):  
V Agnello ◽  
J L Barnes
Keyword(s):  
Rheumatoid Factor ◽  
Primary Structure ◽  
Binding Activity ◽  
Light Chains ◽  
Heat Denaturation ◽  
Antigen Binding ◽  
Rheumatoid Factors ◽  
Simple Method ◽  
Heat Labile

Evidence was obtained that both the WA and BLA crossidiotype (XId) groups are conformational antigens requiring both L and H chains and that with heat denaturation the antigens that define the XIds and antigen-binding activity are lost in parallel. In contrast, the primary structure-dependent crossreactive idiotype (CRI), PSL2, which is only weakly detected on native Wa and Bla monoclonal rheumatoid factors (mRFs), became prominently detected on the heated Wa and Bla mRFs. Heat denaturation may provide a simple method for distinguishing Ids determined by conformational antigen from primary structure-dependent Ids. In addition to heat denaturation, some acid conditions commonly used for preparation of RFs were also found to cause marked loss of Id antigen. The finding of PSL2-CRI on Bla mRF indicates that this Id is not unique to the WA XId.

scholarly journals Variations within oxygen-regulated gene expression in humans

2009 ◽  
Vol 106 (1) ◽  
pp. 212-220 ◽  
Author(s):  
Jerome T. S. Brooks ◽  
Gareth P. Elvidge ◽  
Louisa Glenny ◽  
Jonathan M. Gleadle ◽  
Chun Liu ◽  
...  
Keyword(s):  
Cellular Response ◽  
Genetic Manipulation ◽  
Hypoxia Inducible Factor ◽  
Hereditary Disease ◽  
Peripheral Blood Lymphocytes ◽  
Cellular Level ◽  
Normal Individuals ◽  
Regulated Gene Expression ◽  
Open Question ◽  
Hif Pathway

The effects of hypoxia on gene transcription are mainly mediated by a transcription factor complex termed hypoxia-inducible factor (HIF). Genetic manipulation of animals and studies of humans with rare hereditary disease have shown that modifying the HIF pathway affects systems-level physiological responses to hypoxia. It is, however, an open question whether variations in systems-level responses to hypoxia between individuals could arise from variations within the HIF system. This study sought to determine whether variations in the responsiveness of the HIF system at the cellular level could be detected between normal individuals. Peripheral blood lymphocytes (PBL) were isolated on three separate occasions from each of 10 healthy volunteers. After exposure of PBL to eight different oxygen tensions ranging from 20% to 0.1%, the expression levels of four HIF-regulated transcripts involved in different biological pathways were measured. The profile of expression of all four transcripts in PBL was related to oxygen tension in a curvilinear manner. Double logarithmic transformation of these data resulted in a linear relationship that allowed the response to be parameterized through a gradient and intercept. Analysis of variance (ANOVA) on these parameters showed that the level of between-subject variation in the gradients of the responses that was common across all four HIF-regulated transcripts was significant ( P = 0.008). We conclude that statistically significant variation within the cellular response to hypoxia can be detected between normal humans. The common nature of the variability across all four HIF-regulated genes suggests that the source of this variation resides within the HIF system itself.

Normal individuals with positive tests for rheumatoid factor

1968 ◽  
Vol 11 (1) ◽  
pp. 50-055 ◽  
Author(s):  
Marion Waller ◽  
Elam C. Toone
Keyword(s):  
Rheumatoid Factor ◽  
Normal Individuals

scholarly journals Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

1999 ◽  
Vol 22 (1) ◽  
pp. 17-20
Author(s):  
Magaly M. Sales ◽  
Edmundo J. de Lucca ◽  
Seizo Yamashita ◽  
Luis Henrique Cury Saad
Keyword(s):  
Pilot Study ◽  
Familial Adenomatous Polyposis ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Adenomatous Polyposis ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
Normal Individuals ◽  
G2 Phase

Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Autoreactive lymphocytes in thyroid disorders. Quantitation of anti-thyroglobulin antibody formation by a specific haemolytic plaque forming cell (PFC) assay

1986 ◽  
Vol 113 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Jøgen Petersen ◽  
Ulla Feldt-Rasmussen ◽  
Flemming Larsen ◽  
Kai Siersbæk-Nielsen
Keyword(s):  
Antibody Formation ◽  
Mononuclear Cells ◽  
Matched Control ◽  
Pokeweed Mitogen ◽  
Induced Response ◽  
Thyroid Disorders ◽  
Antigen Specificity ◽  
Thyroglobulin Antibody ◽  
Blood Mononuclear Cells

Abstract. Blood mononuclear cells (MNC) from 21 patients with autoimmune thyroiditis were assayed for secretion of immunoglobulins in vitro by a reverse haemolytic plaque forming cell (PFC) assay. An anti-gen-specific assay was employed to quantify anti-thyroglobulin antibody (TgAb) secreting cells. The sensitivities of the two PFC assays were similar. The antigen specificity of the Tg-PFC assay was demonstrated by the ability of free Tg to inhibit PFC formation. The number of spontaneous TgAb-secreting cells was low (median 3 IgG-Tg-PFC/106, range 0–35/106); TgAb activity was found in 3% (range 0–11%) of total IgG-PFC. The number of spontaneous IgG-TgAb-secreting cells correlated positively to TgAb titres in serum. MNC from most patients secreted IgG-TgAb upon polyclonal stimulation in vitro for six days with pokeweed mitogen (52 IgG-Tg-PFC/106, range 0–478/106); TgAb activity was found among 2% (range 0–8%) of total IgG-PFC. Again, pokeweed mitogen-induced TgAb secretion correlated positively to TgAb titres in serum. Finally, MNC from most patients secreted TgAb after culture with Tg. The Tg-induced response was about 1/3 of the pokeweed mitogen-induced TgAb response. Tg did not increase the production of total IgG indicating that Tg is not a polyclonal stimulus. Few TgAb-secreting MNC were discovered in euthyroid sex and age-matched control patients.

OCCURRENCE OF γ-GLOBULIN COMPLEXES IN SERUM AND JOINT FLUID OF RHEUMATOID ARTHRITIS PATIENTS: USE OF MONOCLONAL RHEUMATOID FACTORS AS REAGENTS FOR THEIR DEMONSTRATION

1971 ◽  
Vol 134 (3) ◽  
pp. 286-295 ◽  
Author(s):  
R. J. Winchester ◽  
H. G. Kunkel ◽  
V. Agnello
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Lupus Erythematosus ◽  
Complement Fixation ◽  
Joint Fluid ◽  
Exact Nature ◽  
Rheumatoid Factors ◽  
Serum Complement ◽  
Systemic Lupus ◽  
Low Incidence

γG globulin complexed in an unusual form has been demonstrated in the serum of many patients with rheumatoid arthritis. Such complexes have been detected and isolated principally through precipitation reactions with monoclonal γM rheumatoid factors. These monoclonal rheumatoid factors exhibited a greater sensitivity to react with small complexes or aggregates of γ-globulin than polyclonal rheumatoid factor from rheumatoid arthritis sera or isolated C1q. The serum complexes consisted in large part of high molecular weight but acid-dissociable 7S γG globulin molecules They however differed from the complexes in the joint fluid by not yielding precipitates with C1q and were not found in association with evidence of marked serum complement fixation or activation. A small number of systemic lupus erythematosus sera, primarily those forming cryoprecipitates, also gave reactions with monoclonal rheumatoid factor. Sera from patients with a variety of nonrheumatic diseases gave a low incidence of reactions. The exact nature of the complexes in the rheumatoid arthritis sera remains somewhat in doubt although γG rheumatoid factors appear partly involved.

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