Immunoglobulin Synthesis in Vitro by Splenic Tissue in Idiopathic Thrombocytopenic Purpura

McMillan, Robert; Longmire, Robert L.; Yelenosky, Robert; Smith, Richard; Craddock, Charles G.

doi:10.1056/nejm197203302861302

Cited by 90 publications

(30 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet involvement in the production of pathogenic antibodies in ITP raises the question of where the interactions between activated platelets and B lymphocytes may take place in vivo. The spleen is considered to be a primary site for antiplatelet antibody production in ITP 2,19,20 and could be where the necessary contact interactions between platelets and B lymphocytes take place. Interestingly, GPIIb/IIIa can be detected within the white pulp follicles in ITP.…”

Section: Resultsmentioning

confidence: 99%

Platelet-associated CD154 in immune thrombocytopenic purpura

Solanilla

Pasquet

Viallard

et al. 2005

Blood

View full text Add to dashboard Cite

Ripoche CD40-ligand (CD154) is expressed on activated CD4 ؉ T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin ␣IIb␤3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease. (Blood. 2005;105:215-218)

show abstract

Section: Resultsmentioning

confidence: 99%

Platelet-associated CD154 in immune thrombocytopenic purpura

Solanilla

Pasquet

Viallard

et al. 2005

Blood

View full text Add to dashboard Cite

show abstract

“…This method was later modified by McMillan et a1 for the detection of platelet-associated IgG [34]. A second competitive binding assay introduced b y Dixon quantitates the inhibition of complement-dependent lysis of sheep erythrocytes by platelet-bound IgC, which is inversely proportional to the platelet count 1231.…”

Section: The Role Of Antibodiesmentioning

confidence: 99%

“…The second role of the spleen, platelet antibody formation, has been determined through studies of McMiIlan in which splenic immunoglobulin synthesis was measured in vitro and found to be five times greater than that of controls [50]. More recently, the spleens of two children with "typical" ITP were studied and were found to have IgG synthesis rates five-and sevenfold greater than normal.…”

Section: The Role Of the Spleenmentioning

confidence: 99%

Acute idiopathic thrombocytopenic purpura in children

McWilliams

Maurer

1979

American J Hematol

View full text Add to dashboard Cite

Acute idiopathic thrombocytopenic purpura (ITP) characteristically follows a viral illness in preschool children. The exact role of viruses in the pathogenesis of this disorder remains uncertain, but the finding of markedly elevated levels of platelet‐associated IgG serves to distinguish it from the chronic form of the disease and permits speculation on the mechanisms of platelet destruction. Although the spleen is important in both antibody production and platelet destruction, bone marrow synthesis of IgG has also been shown to be increased.The clinical course may be alarming, but mortality is low and prognosis excellent. Controversy has surrounded the role of steroids in the management of acute childhood ITP in retrospective studies. Controlled studies, however, indicate that thrombocytopenia is reversed sooner in treated patients.New assays for platelet‐associated IgG offer new insights into this disorder and will allow delineation of acute and chronic disease at the time of diagnosis.

show abstract

“…9 The spleen also serves as a reservoir for long-lived, anti-platelet antibody-producing plasma cells. [10][11][12] Even in the current era, when effective medical therapies for ITP are available, splenectomy is associated with a higher rate of long-term remission than any other ITP therapy, [13][14][15] presumably reflecting removal of the site of platelet clearance and autoantibody production.…”

Section: Introductionmentioning

confidence: 99%

Splenectomy for immune thrombocytopenia: down but not out

Chaturvedi

Arnold

McCrae

2018

Blood

159

154

View full text Add to dashboard Cite

word count: 239Word count: 4298 ABSTRACTSplenectomy is an effective therapy for steroid-refractory or dependent immune thrombocytopenia (ITP). With the advent of medical alternatives such as rituximab and thrombopoietin receptor antagonists (TPO-RA), the use of splenectomy has declined and is generally reserved for patients that fail multiple medical therapies. Splenectomy removes the primary site of platelet clearance and autoantibody production, and offers the highest rate of durable response (50-70%) compared to other ITP therapies. However, there are no reliable predictors of splenectomy response, and long-term risks of infection and cardiovascular complications must be considered. Since the long-term efficacy of different second-line medical therapies for ITP have not been directly compared, treatment decisions must be made without supportive evidence. Splenectomy continues to be a reasonable treatment option for many patients, including those with an active lifestyle who desire freedom from medication and monitoring, and patients with fulminant ITP that does not respond well to medical therapy. We try to avoid splenectomy within the first 12 months after ITP diagnosis for most patients to allow for spontaneous or therapy-induced remissions, particularly in older patients who have increased surgical morbidity and lower rates of response, and in young children. Treatment decisions must be individualized based on patients' comorbidities, lifestyles and preferences. Future research should focus on comparing long-term outcomes of patients treated with different second line therapies, and on developing personalized medicine approaches to identify subsets of patients most likely to respond to splenectomy or other therapeutic approaches.

show abstract

Immunoglobulin Synthesis in Vitro by Splenic Tissue in Idiopathic Thrombocytopenic Purpura

Cited by 90 publications

References 10 publications

Platelet-associated CD154 in immune thrombocytopenic purpura

Platelet-associated CD154 in immune thrombocytopenic purpura

Acute idiopathic thrombocytopenic purpura in children

Splenectomy for immune thrombocytopenia: down but not out

Contact Info

Product

Resources

About