Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia

George, James N.; Saucerman, S

doi:10.1182/blood.v72.1.362.362

Cited by 68 publications

(13 citation statements)

References 12 publications

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“…A positive correlation between serum and platelet values was found in ATP patients, suggesting non-specific absorbtion, but not in the three immune complex thrombocytopenic cohorts. The lack of a positive correlation between serum IgG and PAIgG in ATP patients was consistent with the observations of George & Saucerman (1988), who found no correlation between platelet surface IgG and serum IgG in ATP, dysproteinaemias and normal subjects studied, despite a correlation between their total platelet IgG and serum IgG. However, despite the correlation of serum and total platelet IgG there was no correlation between total platelet IgG and surface IgG.…”

Section: Discussionsupporting

confidence: 90%

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis‐cirrhosis, and HIV‐1 infection by platelet and serum immunological measurements

et al. 1999

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Summary.A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125 I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2·8-, 5·6-and 5·8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients; platelet C3C4 was 3·2-, 4·8-and 4·5-fold higher respectively; platelet IgM was 2·2-, 3·7-and 3·8-fold higher respectively; serum PEG-IC levels were 4·2-, 4·8-and 2·1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r ¼ 0·5, P < 0·04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r ¼ 0·7, P < 0·04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.

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Section: Discussionsupporting

confidence: 90%

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis‐cirrhosis, and HIV‐1 infection by platelet and serum immunological measurements

et al. 1999

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“…l i e immunoglobulins and albumin which are present in the a-granules in similar concentration as in plasma. Concerning fibrinogen, the concentration of which is 10 times higher in the a-granules than in the plasma (George & Saucerman, 1988), recent data have shown that its uptake is receptormediated and can be inhibited by antibody blocking of Gp IIb/IIIa (Harrison et al, 1992) and by barbourin, a desintegrin derived from venom viper which binds to platelet integrin an& (Handagama et al, 1993), showing that the primary receptor that mediates endocytosis for fibrinogen is cq&.…”

Section: Discussionmentioning

confidence: 99%

Absence of incorporation of plasma von Willebrand factor into porcine platelet a‐granules

et al. 1995

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In order to study the relationship between plasma and platelet von Willebrand factor (vWF), we used an experimental model of crossed bone marrow transplantation (BMT) between SLA immunocompatible normal and homozygous von Willebrand (vWD) pigs. A normal pig received bone marrow from a vWD pig and a second pig with vWD was engrafted with marrow from a normal pig. Each recipient, after total irradiation of 10 Grays, received by a central catheter 10(10) monocellular bone marrow cells without immunosuppression. The animals were followed for 50 d and no graft rejection or graft-versus-host disease was observed. After aplasia occurring 3 weeks after BMT, white blood cells and platelets returned to normal. Before transplantation, in the vWD pig, vWFAg and vWF activity were not detected in plasma and in platelet and megakaryocyte alpha-granules. After transplantation with normal marrow, platelet vWFAg and platelet vWF activity wer normal and high molecular weight multimers and numerous tubular structures were present in alpha-granules. Before transplantation, the normal pig had normal plasma and platelet vWFAg-vWF activity, normal multimeric pattern, and the platelet and megakaryocyte alpha-granules displayed many tubular structures, eccentrically located in one of their poles, coinciding with immunogold staining vWFAg. After transplantation with homozygous vWD marrow, platelet and megakaryocyte alpha-granules lacked tubular structures. Alpha-granule immunogold staining for vWF was consistently negative, although plasma vWF was at a normal level. In conclusion, this study shows that, unlike other plasma proteins such as fibrinogen. vWF endocytosis does not occur from plasma to the platelet alpha-granules. Platelet and megakaryocyte vWF solely originates from megakaryocyte endogenous synthesis and is independent of plasma vWF.

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“…We also show, for the first time, that immunoglobulins may be present in human bone marrow MK. Because immunoglobulins enter MK through fluid‐phase endocytosis, the concentration of these molecules in MK is proportional to plasma levels ( George et al , 1990 ), whereas fibrinogen, which enters through receptor‐mediated endocytosis ( George et al , 1990 ; George & Saucerman, 1988; Handagama et al , 1993 ), is highly concentrated. It was therefore of interest to study MK from patients with increased levels of circulating immunoglobulins such as those with multiple myeloma.…”

Section: Discussionmentioning

confidence: 99%

“…This uptake is probably regulated by the integrin receptor α IIb β 3 ( Handagama et al , 1993 , 1995), the platelet receptor for fibrinogen. Other plasma proteins such as immunoglobulins and albumin can also enter MK α‐granules through fluid‐phase endocytosis ( George & Saucerman, 1988; George et al , 1985 ; Handagama et al , 1990 ).…”

mentioning

confidence: 99%

Inverse immunostaining pattern for synthesized versus endocytosed alpha‐granule proteins in human bone marrow megakaryocytes

et al. 1998

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Summary. The time of appearance and pattern of expression of several a-granule proteins, von Willebrand factor (VWF), fibrinogen and immunoglobulins (Ig) were examined and compared in human bone marrow megakaryocytes (MK) using an immunocytochemical approach. VWF is synthesized by immature MK, whereas it has been shown that fibrinogen is incorporated from the plasma into a-granules. The present study was undertaken in order to determine whether there are chronological and morphological differences in the expression of VWF and fibrinogen in vivo in human MK. Seven paraffin-embedded biopsies of normal human bone marrow were labelled with specific antibodies for VWF and for fibrinogen, detected by the alkaline phosphatase antialkaline phosphatase (APAAP) method, and analysed by immunomorphometry. We found a clear, statistically significant, difference in the labelling pattern of VWF and fibrinogen. The expression of other endocytosed a-granule proteins, immunoglobulins G and A, was therefore studied in bone marrow MK from two patients with multiple myeloma, one with monoclonal IgG and one with monoclonal IgA. The immunostaining pattern was similar to that of fibrinogen and different from VWF, and characteristic of endocytosed a-granule proteins.This study demonstrates that: (i) immunohistochemical staining of MK a-granules proteins distinguishes the peripheral cockade distribution pattern of endocytosed protein from the perinuclear pattern of endogenously synthesized proteins; (ii) VWF is present in human bone marrow MK when fibrinogen is not yet detectable; (iii) VWF synthesis ceases while fibrinogen is still being incorporated; (iv) immunoglobulins can be detected in MK cytoplasm, with a staining pattern resembling that of fibrinogen.

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Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia

Cited by 68 publications

References 12 publications

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis‐cirrhosis, and HIV‐1 infection by platelet and serum immunological measurements

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis‐cirrhosis, and HIV‐1 infection by platelet and serum immunological measurements

Absence of incorporation of plasma von Willebrand factor into porcine platelet a‐granules

Inverse immunostaining pattern for synthesized versus endocytosed alpha‐granule proteins in human bone marrow megakaryocytes

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