Phenotype, penetrance, and treatment of 133 cytotoxic
T-lymphocyte antigen 4-insufficient subjects

J 2018

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects

SCHWAB, Charlotte, Annemarie GABRYSCH, Peter OLBRICH, Virginia PATINO, Klaus WARNATZ et. al.

Základní údaje

Originální název

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects

Autoři

SCHWAB, Charlotte (276 Německo), Annemarie GABRYSCH (276 Německo), Peter OLBRICH (724 Španělsko), Virginia PATINO (858 Uruguay), Klaus WARNATZ (276 Německo), Daniel WOLFF (276 Německo), Akihiro HOSHINO (392 Japonsko), Masao KOBAYASHI (392 Japonsko), Kohsuke IMAI (392 Japonsko), Masatoshi TAKAGI (392 Japonsko), Ingunn DYBEDAL (578 Norsko), Jamanda A. HADDOCK (826 Velká Británie a Severní Irsko), David M. SANSOM (826 Velká Británie a Severní Irsko), Jose M. LUCENA (724 Španělsko), Maximilian SEIDL (276 Německo), Annette SCHMITT-GRAEFF (276 Německo), Veronika REISER (276 Německo), Florian EMMERICH (276 Německo), Natalie FREDE (276 Německo), Alla BULASHEVSKA (276 Německo), Ulrich SALZER (276 Německo), Desiree SCHUBERT (276 Německo), Seiichi HAYAKAWA (392 Japonsko), Satoshi OKADA (392 Japonsko), Maria KANARIOU (300 Řecko), Zeynep Yesim KUCUK (840 Spojené státy), Hugo CHAPDELAINE (124 Kanada), Lenka PETRUZELKOVA (203 Česká republika), Zdenek SUMNIK (203 Česká republika), Anna SEDIVA (203 Česká republika), Mary SLATTER (826 Velká Británie a Severní Irsko), Peter D. ARKWRIGHT (826 Velká Británie a Severní Irsko), Andrew CANT (826 Velká Británie a Severní Irsko), Hanns-Martin LORENZ (276 Německo), Thomas GIESE (276 Německo), Vassilios LOUGARIS (380 Itálie), Alessandro PLEBANI (380 Itálie), Christina PRICE (840 Spojené státy), Kathleen E. SULLIVAN (840 Spojené státy), Michel MOUTSCHEN (56 Belgie), Jiří LITZMAN (203 Česká republika, domácí), Tomáš FREIBERGER (203 Česká republika, domácí), Frank L. VAN DE VEERDONK (528 Nizozemské království), Mike RECHER (756 Švýcarsko), Michael H. ALBERT (276 Německo), Fabian HAUCK (276 Německo), Suranjith SENEVIRATNE (826 Velká Británie a Severní Irsko), Jana Pachlopnik SCHMID (756 Švýcarsko), Antonios KOLIOS (756 Švýcarsko), Gary UNGLIK (36 Austrálie), Christian KLEMANN (276 Německo), Carsten SPECKMANN (276 Německo), Stephan EHL (276 Německo), Alan LEICHTNER (840 Spojené státy), Richard BLUMBERG (840 Spojené státy), Andre FRANKE (276 Německo), Scott SNAPPER (840 Spojené státy), Sebastian ZEISSIG (276 Německo), Charlotte CUNNINGHAM-RUNDLES (840 Spojené státy), Lisa GIULINO-ROTH (840 Spojené státy), Oliver ELEMENTO (840 Spojené státy), Gregor DUCKERS (276 Německo), Tim NIEHUES (276 Německo), Eva FRONKOVA (203 Česká republika), Veronika KANDEROVA (203 Česká republika), Craig D. PLATT (840 Spojené státy), Janet CHOU (840 Spojené státy), Talal A. CHATILA (840 Spojené státy), Raif GEHA (840 Spojené státy), Elizabeth MCDERMOTT (826 Velká Británie a Severní Irsko), Su BUNN (826 Velká Británie a Severní Irsko), Monika KURZAI (276 Německo), Ansgar SCHULZ (276 Německo), Laia ALSINA (724 Španělsko), Ferran CASALS (724 Španělsko), Angela DEYA-MARTINEZ (724 Španělsko), Sophie HAMBLETON (826 Velká Británie a Severní Irsko), Hirokazu KANEGANE (392 Japonsko), Kjetil TASKEN (578 Norsko), Olaf NETH (724 Španělsko) a Bodo GRIMBACHER (276 Německo, garant)

Vydání

Journal of allergy and clinical immunology, New York, Mosby-Elsevier, 2018, 0091-6749

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30225 Allergy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 14.110

Kód RIV

RIV/00216224:14110/18:00105160

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.jaci.2018.02.055

UT WoS

000452315800026

Klíčová slova anglicky

Cytotoxic T-lymphocyte antigen 4; primary immunodeficiency; autoimmunity; hypogammaglobulinemia; hematopoietic stem cell transplantation; abatacept; sirolimus; immune dysregulation; common variable immunodeficiency

Štítky

14110114, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 3. 2019 15:48, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affectedmutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

Citovat

SCHWAB, Charlotte, Annemarie GABRYSCH, Peter OLBRICH, Virginia PATINO, Klaus WARNATZ, Daniel WOLFF, Akihiro HOSHINO, Masao KOBAYASHI, Kohsuke IMAI, Masatoshi TAKAGI, Ingunn DYBEDAL, Jamanda A. HADDOCK, David M. SANSOM, Jose M. LUCENA, Maximilian SEIDL, Annette SCHMITT-GRAEFF, Veronika REISER, Florian EMMERICH, Natalie FREDE, Alla BULASHEVSKA, Ulrich SALZER, Desiree SCHUBERT, Seiichi HAYAKAWA, Satoshi OKADA, Maria KANARIOU, Zeynep Yesim KUCUK, Hugo CHAPDELAINE, Lenka PETRUZELKOVA, Zdenek SUMNIK, Anna SEDIVA, Mary SLATTER, Peter D. ARKWRIGHT, Andrew CANT, Hanns-Martin LORENZ, Thomas GIESE, Vassilios LOUGARIS, Alessandro PLEBANI, Christina PRICE, Kathleen E. SULLIVAN, Michel MOUTSCHEN, Jiří LITZMAN, Tomáš FREIBERGER, Frank L. VAN DE VEERDONK, Mike RECHER, Michael H. ALBERT, Fabian HAUCK, Suranjith SENEVIRATNE, Jana Pachlopnik SCHMID, Antonios KOLIOS, Gary UNGLIK, Christian KLEMANN, Carsten SPECKMANN, Stephan EHL, Alan LEICHTNER, Richard BLUMBERG, Andre FRANKE, Scott SNAPPER, Sebastian ZEISSIG, Charlotte CUNNINGHAM-RUNDLES, Lisa GIULINO-ROTH, Oliver ELEMENTO, Gregor DUCKERS, Tim NIEHUES, Eva FRONKOVA, Veronika KANDEROVA, Craig D. PLATT, Janet CHOU, Talal A. CHATILA, Raif GEHA, Elizabeth MCDERMOTT, Su BUNN, Monika KURZAI, Ansgar SCHULZ, Laia ALSINA, Ferran CASALS, Angela DEYA-MARTINEZ, Sophie HAMBLETON, Hirokazu KANEGANE, Kjetil TASKEN, Olaf NETH a Bodo GRIMBACHER. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. Journal of allergy and clinical immunology. New York: Mosby-Elsevier, 2018, roč. 142, č. 6, s. 1932-1946. ISSN 0091-6749. Dostupné z: https://dx.doi.org/10.1016/j.jaci.2018.02.055.

@article{1482539,
   author = {Schwab, Charlotte and Gabrysch, Annemarie and Olbrich, Peter and Patino, Virginia and Warnatz, Klaus and Wolff, Daniel and Hoshino, Akihiro and Kobayashi, Masao and Imai, Kohsuke and Takagi, Masatoshi and Dybedal, Ingunn and Haddock, Jamanda A. and Sansom, David M. and Lucena, Jose M. and Seidl, Maximilian and SchmittandGraeff, Annette and Reiser, Veronika and Emmerich, Florian and Frede, Natalie and Bulashevska, Alla and Salzer, Ulrich and Schubert, Desiree and Hayakawa, Seiichi and Okada, Satoshi and Kanariou, Maria and Kucuk, Zeynep Yesim and Chapdelaine, Hugo and Petruzelkova, Lenka and Sumnik, Zdenek and Sediva, Anna and Slatter, Mary and Arkwright, Peter D. and Cant, Andrew and Lorenz, HannsandMartin and Giese, Thomas and Lougaris, Vassilios and Plebani, Alessandro and Price, Christina and Sullivan, Kathleen E. and Moutschen, Michel and Litzman, Jiří and Freiberger, Tomáš and van de Veerdonk, Frank L. and Recher, Mike and Albert, Michael H. and Hauck, Fabian and Seneviratne, Suranjith and Schmid, Jana Pachlopnik and Kolios, Antonios and Unglik, Gary and Klemann, Christian and Speckmann, Carsten and Ehl, Stephan and Leichtner, Alan and Blumberg, Richard and Franke, Andre and Snapper, Scott and Zeissig, Sebastian and CunninghamandRundles, Charlotte and GiulinoandRoth, Lisa and Elemento, Oliver and Duckers, Gregor and Niehues, Tim and Fronkova, Eva and Kanderova, Veronika and Platt, Craig D. and Chou, Janet and Chatila, Talal A. and Geha, Raif and McDermott, Elizabeth and Bunn, Su and Kurzai, Monika and Schulz, Ansgar and Alsina, Laia and Casals, Ferran and DeyaandMartinez, Angela and Hambleton, Sophie and Kanegane, Hirokazu and Tasken, Kjetil and Neth, Olaf and Grimbacher, Bodo},
   article_location = {New York},
   article_number = {6},
   doi = {http://dx.doi.org/10.1016/j.jaci.2018.02.055},
   keywords = {Cytotoxic T-lymphocyte antigen 4; primary immunodeficiency; autoimmunity; hypogammaglobulinemia; hematopoietic stem cell transplantation; abatacept; sirolimus; immune dysregulation; common variable immunodeficiency},
   language = {eng},
   issn = {0091-6749},
   journal = {Journal of allergy and clinical immunology},
   title = {Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects},
   volume = {142},
   year = {2018}
}

TY  - JOUR
ID  - 1482539
AU  - Schwab, Charlotte - Gabrysch, Annemarie - Olbrich, Peter - Patino, Virginia - Warnatz, Klaus - Wolff, Daniel - Hoshino, Akihiro - Kobayashi, Masao - Imai, Kohsuke - Takagi, Masatoshi - Dybedal, Ingunn - Haddock, Jamanda A. - Sansom, David M. - Lucena, Jose M. - Seidl, Maximilian - Schmitt-Graeff, Annette - Reiser, Veronika - Emmerich, Florian - Frede, Natalie - Bulashevska, Alla - Salzer, Ulrich - Schubert, Desiree - Hayakawa, Seiichi - Okada, Satoshi - Kanariou, Maria - Kucuk, Zeynep Yesim - Chapdelaine, Hugo - Petruzelkova, Lenka - Sumnik, Zdenek - Sediva, Anna - Slatter, Mary - Arkwright, Peter D. - Cant, Andrew - Lorenz, Hanns-Martin - Giese, Thomas - Lougaris, Vassilios - Plebani, Alessandro - Price, Christina - Sullivan, Kathleen E. - Moutschen, Michel - Litzman, Jiří - Freiberger, Tomáš - van de Veerdonk, Frank L. - Recher, Mike - Albert, Michael H. - Hauck, Fabian - Seneviratne, Suranjith - Schmid, Jana Pachlopnik - Kolios, Antonios - Unglik, Gary - Klemann, Christian - Speckmann, Carsten - Ehl, Stephan - Leichtner, Alan - Blumberg, Richard - Franke, Andre - Snapper, Scott - Zeissig, Sebastian - Cunningham-Rundles, Charlotte - Giulino-Roth, Lisa - Elemento, Oliver - Duckers, Gregor - Niehues, Tim - Fronkova, Eva - Kanderova, Veronika - Platt, Craig D. - Chou, Janet - Chatila, Talal A. - Geha, Raif - McDermott, Elizabeth - Bunn, Su - Kurzai, Monika - Schulz, Ansgar - Alsina, Laia - Casals, Ferran - Deya-Martinez, Angela - Hambleton, Sophie - Kanegane, Hirokazu - Tasken, Kjetil - Neth, Olaf - Grimbacher, Bodo
PY  - 2018
TI  - Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects
JF  - Journal of allergy and clinical immunology
VL  - 142
IS  - 6
SP  - 1932-1946
EP  - 1932-1946
PB  - Mosby-Elsevier
SN  - 00916749
KW  - Cytotoxic T-lymphocyte antigen 4
KW  - primary immunodeficiency
KW  - autoimmunity
KW  - hypogammaglobulinemia
KW  - hematopoietic stem cell transplantation
KW  - abatacept
KW  - sirolimus
KW  - immune dysregulation
KW  - common variable immunodeficiency
N2  - Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affectedmutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.
ER  -

SCHWAB, Charlotte, Annemarie GABRYSCH, Peter OLBRICH, Virginia PATINO, Klaus WARNATZ, Daniel WOLFF, Akihiro HOSHINO, Masao KOBAYASHI, Kohsuke IMAI, Masatoshi TAKAGI, Ingunn DYBEDAL, Jamanda A. HADDOCK, David M. SANSOM, Jose M. LUCENA, Maximilian SEIDL, Annette SCHMITT-GRAEFF, Veronika REISER, Florian EMMERICH, Natalie FREDE, Alla BULASHEVSKA, Ulrich SALZER, Desiree SCHUBERT, Seiichi HAYAKAWA, Satoshi OKADA, Maria KANARIOU, Zeynep Yesim KUCUK, Hugo CHAPDELAINE, Lenka PETRUZELKOVA, Zdenek SUMNIK, Anna SEDIVA, Mary SLATTER, Peter D. ARKWRIGHT, Andrew CANT, Hanns-Martin LORENZ, Thomas GIESE, Vassilios LOUGARIS, Alessandro PLEBANI, Christina PRICE, Kathleen E. SULLIVAN, Michel MOUTSCHEN, Jiří LITZMAN, Tomáš FREIBERGER, Frank L. VAN DE VEERDONK, Mike RECHER, Michael H. ALBERT, Fabian HAUCK, Suranjith SENEVIRATNE, Jana Pachlopnik SCHMID, Antonios KOLIOS, Gary UNGLIK, Christian KLEMANN, Carsten SPECKMANN, Stephan EHL, Alan LEICHTNER, Richard BLUMBERG, Andre FRANKE, Scott SNAPPER, Sebastian ZEISSIG, Charlotte CUNNINGHAM-RUNDLES, Lisa GIULINO-ROTH, Oliver ELEMENTO, Gregor DUCKERS, Tim NIEHUES, Eva FRONKOVA, Veronika KANDEROVA, Craig D. PLATT, Janet CHOU, Talal A. CHATILA, Raif GEHA, Elizabeth MCDERMOTT, Su BUNN, Monika KURZAI, Ansgar SCHULZ, Laia ALSINA, Ferran CASALS, Angela DEYA-MARTINEZ, Sophie HAMBLETON, Hirokazu KANEGANE, Kjetil TASKEN, Olaf NETH a Bodo GRIMBACHER. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. \textit{Journal of allergy and clinical immunology}. New York: Mosby-Elsevier, 2018, roč.~142, č.~6, s.~1932-1946. ISSN~0091-6749. Dostupné z: https://dx.doi.org/10.1016/j.jaci.2018.02.055.

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