Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members

Kogawa, Kazuhiro; Lee, Susan M.; Villanueva, Joyce; Marmer, Daniel J.; Sümegi, János; Filipovich, Alexandra H.

doi:10.1182/blood.v99.1.61

Cited by 227 publications

(194 citation statements)

References 17 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…in 35AE7% of the HLH patients studied. This incidence is comparable to previous estimates of the prevalence of perforin abnormalities (Stepp et al, 1999;Clementi et al, 2001;Ericson et al, 2001;Kogawa et al, 2002;Suga et al, 2002). Two of the mutations occurred in more than one patient, namely, 1090-1091delCT and 207delC.…”

Section: Discussionsupporting

confidence: 76%

“…However, it was found that age at diagnosis, which tended to be similar for the members of the same family, was delayed in the patients from two families with missense mutations. These observations are supported by the fact that the single HLH patient we identified with a perforin gene missense mutation was diagnosed at 11 years Stepp et al (1999), Clementi et al (2001Clementi et al ( , 2002, Ericson et al (2001), Kogawa et al (2002), Feldmann et al (2002, Suga et al (2002) and the present study. The upper panel represents perforin gene mutations reported in this study and the lower panel lists those that have been previously described.…”

Section: Discussionsupporting

confidence: 75%

“…In contrast, Kogawa et al (2002), who used four-colour flow cytometric analysis, demonstrated that the perforin expression of CD8 + cells in children aged 0-1 years and 1-15 years constituted 0-3% and 2-11% of the total lymphocyte population respectively. They also found that perforin expression of CD56 + cells constituted 4-30% and 12-34% of all lymphocytes in those aged 0-1 years and 1-15 years.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan

Ueda¹,

Morimoto²,

Inaba

et al. 2003

Br J Haematol

View full text Add to dashboard Cite

Summary. Perforin gene (PRF1) mutations appear to occur in about 30% of patients with haemophagocytic lymphohistiocytosis (HLH). We tested perforin expression and gene mutations in 14 HLH patients and six patients with EpsteinBarr virus-associated HLH (EBV-HLH) in Japan. Five of the 14 HLH patients had perforin abnormalities. The presence of PRF1 genetic abnormality correlated well with the lack of perforin expression as determined by flow cytometry. Sequencing showed that four patients had a compound heterozygous mutation while the fifth patient had a homozygous mutation. Three of the mutations we detected were novel. In contrast, none of the six EBV-HLH patients showed perforin abnormalities. Our data, combined with the PRF1 mutations in three previously reported Japanese patients, suggest that the 1090-1091delCT and 207delC mutations of the perforin gene are frequently present in Japanese HLH patients (62AE5% and 37AE5% respectively). Examination of the geographical origins of the ancestors in the perforin-mutant HLH patients revealed that they mostly came from the Western part of Japan, suggesting that the present-day cases may largely derive from a common ancestor.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan

Ueda¹,

Morimoto²,

Inaba

et al. 2003

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…3 Familyal HLH'e sebep olan şimdiye kadar dört tane mutasyon bildirilmiştir; bunlar PRF1(FHL2), UNC13D (FHL3), STX11 (FHL4) ve STXBP2 (FHL5)'tir.…”

Section: Discussionunclassified

Two Cases with Familial Hemophagocytic Lymphohistiocytosis

Geylan¹,

Karaman²,

Çetin³

2018

Turkiye Klinikleri J Pediatr

View full text Add to dashboard Cite

“…1,8 Perforin staining in cytotoxic cells by flow cytometry has been used as a screening test to identify children with familial HLH, who can then be subjected to genetic analysis. 9,10 The present case fulfilled six out of the eight criteria mentioned in HLH-2004. 1 The clinical features of HLH are fever, hepatosplenomegaly, bleeding manifestations, lymphadenopathy, skin rash, shock, jaundice, central nervous system (CNS) manifestations, renal failure and arthritis.…”

Section: Discussionmentioning

confidence: 99%

Haemophagocytic lymphohistiocytosis

Manohar¹,

Patnayak²,

Kumar³

et al. 2014

J Clin Sci Res

View full text Add to dashboard Cite

We describe a 15-month-old child who presented with a history of fever for the preeding two days and multiple episodes of seizures of one day duration. Physical examination revealed generalized lymphadenopathy and hepatosplenomegaly. The child developed erythematous maculopapular rash, hypotension and required tracheal intubation and mechanical ventilation. Bone marrow aspiration confirmed the diagnosis of hemophagocytic lymphohistiocytosis (HLH). He was treated with dexamethasone, etoposide and cyclosporine, recovered and is doing well on follow-up. HLH is a rare haematological disorder involving the mononuclear phagocyte system. Since it mimics other disorders, its timely diagnosis remains a challenge. It is an aggressive and potential fatal disease of infancy and childhood, if left untreated. HLH may mimic a number of systemic infections thereby causing difficulty in early diagnosis.

show abstract

Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members

Cited by 227 publications

References 17 publications

Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan

Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan

Two Cases with Familial Hemophagocytic Lymphohistiocytosis

Haemophagocytic lymphohistiocytosis

Contact Info

Product

Resources

About