Günlük Klinik Rutinde Sık Kullanılan Basit Laboratuvar Testlerinden (Primer) İmmün Yetmezlik Hastalığına Yaklaşım

Yıl 2019, Cilt: 17 Sayı: 1, 157 - 169, 01.04.2019

Öner Özdemir

Öz

Primer immnünyetmezlik hastalığı
(PİYH) bağışıklık sisteminin değişik unsurlarının doğumsal bozukluklarına bağlı
meydana gelen bozukluklardır. PİYH enfeksiyona eğilimle sonuçlanır ve sıklıkla
otoimmüniteye ve/veya immünregülasyon bozukluğu yatkınlığa eşlik eder. Üç yüz
otuzdan daha fazla PİYH tanımlanmıştır ve bunların 320’den fazlasının moleküler
temeli belirlenmiştir. İçlerinde primer antikor eksiklikleri en sık rastlanan
gruptur ve yaklaşık PİYH’nin yarısından fazlasında bulunur. Artan oranda geç
başlangıçlı vakalar tanınmasına rağmen, PİYH klinik bulguları tipik olarak
yaşamın erken döneminde görülmektedir. Hastalar klinikte genellikle
tekrarlayan, ciddi enfeksiyonlar veya her ikisiyle beraber ve değişik PİYH
ilişkili otoimmünite gelişimiyle karşımıza çıkar. Zamanında teşhis hastanın
özel tedavi merkezlerine gönderilmesi ve kök hücre transplantasyonu dahil uygun
tedavinin hemen başlaması için kaçınılmazdır. Sonuçta, PİYH’in erken teşhisi
optimal bakım ve düzelmiş sürvi (sonuçlar) için esastır. Bu derlemede, en sık
görülen PİYH’lerin araştırılması için temel bir yaklaşım, tipik bazı klinik
bulgular ve en uygun laboratuar tetkikleri basit tam kan sayımından ileri nesil
dizileme gibi genetik testlere kadar, anlatılmaktadır.

Anahtar Kelimeler

Primer immünyetmezlik hastalığı, kombine immünyetmezlik, ağır kombine immünyetmezlik, teşhis, tedavi

Approach to Primary Immunodeficiency Disease from Frequently used Simple Laboratory Tests in a Daily Clinic Routine

Öz

Primary immune deficiency disease
(PIDD) is a hereditary disorder, attributable to inherent defects in diverse
elements of the immune system. PIDD causes susceptibility to infections and is
frequently associated with a tendency to autoimmunity and/or immune
dysregulation. Up-to-date, more than 330 PIDD have been defined and the
molecular (genetic) origins for more than 320 of them are described. In this
group, primary antibody deficiencies are the most common group and
approximately 50% of PIDD patients have this defect. Clinical findings of PIDD
typically appear early in life, although cases with delayed onset are
progressively more documented. Affected PIDD patients usually manifest in
clinic with recurrent infections, severe infections, or both, plus autoimmunity
development that are accompanied with most of the PIDD. Timely diagnosis is
indispensable for transferring patients to specialized centers and the
commencement of proper treatment including stem cell transplantation.
Consequently, the prompt diagnosis of PIDD is necessary for best possible
management and better outcomes. In this review, a basic approach for the
exploration of the most common PIDDs is described, outlining some of the
typical clinical findings and most appropriate laboratory investigations from
simple complete blood count to advanced genetic tests such as next generation
sequencing.

Anahtar Kelimeler

Primary immunodeficiency disease, combined immunodeficiency, severe combined immunodeficiency, diagnosis, treatment

Kaynakça

• 1- Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol 2018; 38(1):129-43.
• 2- Parvaneh N, Casanova JL, Notarangelo LD, Conley ME. Primary immunodeficiencies: a rapidly evolving story. J Allergy Clin Immunol 2013;131(2):314-23.
• 3- Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol 2010; 125(2 Suppl 2): S182-94.
• 4- Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol 2005; 94(5 Suppl 1):S1-63.
• 5- Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015; 136(5): 1186-205.e1-78.
• 6- Kilic SS, Ozel M, Hafizoglu D, Karaca NE, Aksu G, Kutukculer N. The prevalences [correction] and patient characteristics of primary immunodeficiency diseases in Turkey--two centers study. J Clin Immunol 2013; 33(1):74-83.
• 7- 10 Warning Signs - JMF - Jeffrey Modell Foundation Medical advisory Board. Available from: URL: http://www.info4pi.org/library/educational-materials/10-warning-signs
• 8- Chinen J, Paul ME, Shearer WT. Approach to the Evaluation of the immunodeficient patient. In: Rich RR, Fleisher TA, Shearer WT, Schroeder HW Jr, Frew A, Weyand C, editors. Clinical immunology: principles and practice. London: Elsevier; 2012. pp. 1-31.
• 9- Kılıç M, Taşkın E, Selmanoğlu A. Primer İmmün yetmezlikli olgularımızın retrospektif değerlendirilmesi. Fırat Tıp Derg 2015; 20(1): 37-42.
• 10- Aldırmaz S, Yücel E, Kıykım A, Çokuğraş H, Akçakaya N, Camcıoğlu Y. Profile of the patients who present to immunology outpatient clinics because of frequent infections. Turk Ped Archiv 2014; 49:210-6. 11- Uygun DFK, Hafızoğlu D. Primer immün yetmezlik hastalarımızın primer immune yetmezlik hastalarımızın retrospektif değerlendirilmesi; Erzurum deneyimi retrospektif değerlendirilmesi; Erzurum deneyimi. Asthma Allergy Immunol 2015; 13:90-3.
• 12- Misirlioğlu ED, Tayfur G, Doğru M, Duman H, Özmen S, Aytekin C, et al. Allerji kliniğinde izlenen hastalarda primer antikor eksiklikleri. Türkiye Çocuk Hast Derg 2010; 4(4): 219-23.
• 13- Nima Rezaei, Asghar Aghamohammadi, Luigi D. Notarangelo (Eds.)Primary Immunodeficiency Diseases. Berlin: Springer; 2008.
• 14- Pannicke U, Honig M, Hess I, Friesen C, Holzmann K, Rump EM, et al. Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. Nat Genet 2009;41:101-5.
• 15- Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol 2013;20:16-25.
• 16- Oliveira JB, Fleisher TA. Laboratory evaluation of primary immunodeficiencies. J Allergy Clin Immunol 2010;125(2 Suppl 2):S297-305.
• 17- Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, et al. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the primary immune deficiency treatment consortium experience. J Allergy Clin Immunol 2014;133:1092-8.
• 18- Notarangelo LD, Fischer A, Geha RS, Casanova J-L, Chapel H, Conley ME, et al. (International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies). Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol 2009;124:1161-78.
• 19- Kıykım A, Yüce EG, Barış E, Nain E, Keleş S, Aktürk H, et al. Serum IgE düzeyi ve eozinofil sayısı ile atopik hastalıklar hiper IgE sendromu’ndan ayırt edilebilir mi? Asthma Allergy Immunol 2017;15:73-81.
• 20- Routes J, Abinun M, Al-Herz W, Bustamante J, Condino-Neto A, De La Morena MT, et al. ICON: the early diagnosis of congenital immunodeficiencies. J Clin Immunol. 2014; 34(4): 398-424.
• 21- Ochs HD, Slichter SJ, Harker LA, Von Behrens WE, Clark RA, Wedgwood RJ. The Wiskott-Aldrich syndrome: studies of lymphocytes, granulocytes, and platelets. Blood 1980; 55(2):243–52.
• 22- Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T, Durie D, et al. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood 2014;124:2867-71.
• 23-Trakadis YJ, Alfares A, Bodamer OA, Buyukavci M, Christodoulou J, Connor P, et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis 2014; 37:461-73.
• 24- Kishimoto K, Kobayashi R, Sano H, Suzuki D, Maruoka H, Yasuda K, et al. Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption. Clin Immunol 2014;153:17-22.
• 25- Hsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE, Patel SY, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011;118: 2653-5.
• 26- Sassi A, Lazaroski S, Wu G, Haslam SM, Fliegauf M, Mellouli F, et al. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol 2014;133:1410-9, e1-13.
• 27- Balloch A, Licciardi PV, Tang ML. Serotype-specific anti-pneumococcal IgG and immune competence: critical differences in interpretation criteria when different methods are used. J Clin Immunol. 2013; 33(2):335-41.
• 28- Fong SW, Quaqundah BY, Taylor WF. Transfusion 1974; 14: 551-9.
• 29- Shearer WT, Buckley RH, Engler RJM, Finn AF, Fleisher TA, Freeman TM, et al. (CLIC-AAAAI Members). Practice parameters for the diagnosis and management of immuno-deficiency. Ann Allergy Asthma Immunol 1996; 282-94.
• 30- Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, et al. An autoinflammatory disease with deficiency of the interleukin-1receptor antagonist. N Engl J Med 2009; 360:2426-37.
• 31- Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, et al. Interleukin36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365: 620-8.
• 32- Papadaki ME, Lietman SA, Levine MA, Olsen BR, Kaban LB, Reichenberger EJ. Cherubism: best clinical practice. Orphanet J Rare Dis 2012;7(suppl 1):S6.
• 33- Özdemir Ö, Karavaizoğlu Ç. Akım sitometrinin immünolojik ve allerjik hastalıklarda kullanımı. Asthma Allergy Immunol 2016;14:117-28
• 34-Futatani T, Miyawaki T, Tsukada S, Hashimoto S, Kunikata T, Arai S, et al. Deficient expression of Bruton's tyrosine kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and its clinical application to carrier detection. Blood 1998; 91(2):595-602.
• 35- Qamar N, Fuleihan RL. The hyper IgM syndromes. Clin Rev Allergy Immunol 2014; 46:120-30.
• 36- Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N. Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant 2009;15:84-90.
• 37- Ozdemir O, Ravindranath Y, Savaşan S. Cell-mediated cytotoxicity evaluation using monoclonalantibody staining for target or effector cells with annexinV/ propidium iodide colabeling by fluorosphere-adjusted counts on three-color flow cytometry. Cytometry A. 2003; 56(1):53-60.
• 38- Nauseef WM. Diagnostic assays for myeloperoxidase and myeloperoxidase deficiency. Methods Mol Biol 2014;1124:537-46.
• 39- Hagleitner MM, Lankester A, Maraschio P, Hulten M, Fryns JP, Schuetz C, et al. Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). J Med Genet 2008; 45:93-9.
• 40- Devriendt K, Swillen A, Fryns JP. Deletion in chromosome region 22q11 in a child with CHARGE association. Clin Genet 1998; 53(5):408-10.
• 41- Alroqi FJ, Charbonnier LM, Keles S, Ghandour F, Mouawad P, Sabouneh R, et al. DOCK8 Deficiency Presenting as an IPEX-Like Disorder. J Clin Immunol 2017;37(8):811-9.
• 42- Bayer DK, Martinez CA, Sorte HS, Forbes LR, Demmler-Harrison GJ, Hanson IC, et al. Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray. Clin Exp Immunol 2014;178(3):459-69.
• 43- Seleman M, Hoyos-Bachiloglu R, Geha RS, Chou J. Uses of next-generation sequencing technologies for the diagnosis of primaryimmunodeficiencies. Front Immunol 2017; 8: 847.
• 44- Conley ME, Casanova JL. Discovery of single-gene inborn errors of immunity by next generation sequencing. Curr Opin Immunol 2014; 30:17-23.
• 45- Stiehm ER. Immunodeficiency disorders: general considerations. In: Stiehm ER, ed. Immunologic Disorders in Infants and Children. Philadelphia: W B Saunders Co., 1989:157–95.
• 46- Hirschorn R. Adenosine deaminase deficiency. Immunodef Rev 1990; 2:175–98.
• 47- Özdemir O. Neonatal screening test for severe combined immunodeficiency of primary immunodeficiency diseases: TREC assay and its limitations. MOJ Immunol 2016; 3(6): 00107.
• 48- King JR, Hammarström L. Newborn screening for primary immunodeficiency diseases: history, current and future practice. J Clin Immunol 2018; 38(1):56-66.