Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome

Jaroslaw P. Maciejewski, Dean Follmann, Ryotaro Nakamura, Yogen Saunthararajah, Candido E Rivera, Toni Simonis, Kevin E. Brown, John A. Barrett, Neal S. Young

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Abstract

Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.

Original languageEnglish (US)
Pages (from-to)3513-3519
Number of pages7
JournalBlood
Volume98
Issue number13
DOIs
StatePublished - Dec 15 2001
Externally publishedYes

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HLA-DR2 Antigen
Paroxysmal Hemoglobinuria
Aplastic Anemia
Bone
Clone Cells
Proteins
Myelodysplastic Syndromes
Blood
Bone Marrow
Alleles
Immune System Diseases
Granulocytes
Immunosuppression
Autoimmune Diseases

ASJC Scopus subject areas

  • Hematology

Cite this

Maciejewski, J. P., Follmann, D., Nakamura, R., Saunthararajah, Y., Rivera, C. E., Simonis, T., ... Young, N. S. (2001). Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood, 98(13), 3513-3519. https://doi.org/10.1182/blood.V98.13.3513

Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. / Maciejewski, Jaroslaw P.; Follmann, Dean; Nakamura, Ryotaro; Saunthararajah, Yogen; Rivera, Candido E; Simonis, Toni; Brown, Kevin E.; Barrett, John A.; Young, Neal S.

In: Blood, Vol. 98, No. 13, 15.12.2001, p. 3513-3519.

Research output: Contribution to journalArticle

Maciejewski, JP, Follmann, D, Nakamura, R, Saunthararajah, Y, Rivera, CE, Simonis, T, Brown, KE, Barrett, JA & Young, NS 2001, 'Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome', Blood, vol. 98, no. 13, pp. 3513-3519. https://doi.org/10.1182/blood.V98.13.3513
Maciejewski, Jaroslaw P. ; Follmann, Dean ; Nakamura, Ryotaro ; Saunthararajah, Yogen ; Rivera, Candido E ; Simonis, Toni ; Brown, Kevin E. ; Barrett, John A. ; Young, Neal S. / Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. In: Blood. 2001 ; Vol. 98, No. 13. pp. 3513-3519.
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abstract = "Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58{\%} versus 28{\%}; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56{\%}) than in AA without a PNH clone (37{\%}; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50{\%} of responders versus 34{\%} of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.",
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AU - Saunthararajah, Yogen

AU - Rivera, Candido E

AU - Simonis, Toni

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AU - Barrett, John A.

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N2 - Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.

AB - Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.

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