Immunological Evaluation in Patients with Familial Mediterranean fever

Shams Kholoussi; Naglaa Kholoussi; Moushira Erfan Zaki; Hala T. El-Bassyouni; Hala Elnady; Botros Morcos; Asem Aboâ€“Shanab

doi:10.3889/oamjms.2018.079

Authors

Shams Kholoussi National Research Centre - Immunogenetics Department, Cairo
Naglaa Kholoussi National Research Centre - Immunogenetics Department, Cairo
Moushira Erfan Zaki National Research Centre - Biological Anthropology Department, Cairo
Hala T. El-Bassyouni National Research Centre - Clinical Genetics Department, Cairo
Hala Elnady National Research Centre - Child Health, Cairo
Botros Morcos National Research Centre - Immunogenetics Department, Cairo
Asem Aboâ€“Shanab National Research Centre - Immunogenetics Department, Cairo

DOI:

https://doi.org/10.3889/oamjms.2018.079

Keywords:

Flow cytometer, Lymphocytes, NK, Immunoglobulins, Nephelometry, FMF, N/L ratio

Abstract

OBJECTIVE: This study aimed to investigate T & B lymphocyte subsets and Natural Killer (NK) cells patterns in children with FMF versus normal control subjects, to estimate the immunoglobulins IgG, IgM, and IgA levels, and to scrutinize the possible use of Neutrophil / Lymphocyte ratio (NLR) as a marker for subclinical inflammation in FMF patients.

PATIENTS AND METHODS: A group of 42 patients with FMF attending the Genetics Clinic at National Research Centre were included in this study. They were 13 males and 19 females; their age ranged from 2 to 17 years old. Normal healthy subjects within the same age and sex range were included as a control group. Complete blood picture was done for all cases, and neutrophil/ lymphocyte ratio was calculated. Flow cytometer analysis was done for CD3, CD4, CD8, CD19 and CD16 using monoclonal antibodies. Immunoglobulins IgG, IgA and IgM were estimated in serum using nephelometry.

RESULTS: Positive consanguinity was present in 20 patients (47.6%). Abdominal pain was the most common manifestation followed by fever, arthritis, and red rash. CD3, CD4 and CD8 were statistically increased in patients group as compared to normal control group, while CD16 was statistically decreased.

CONCLUSION: The study suggests that quantitative measurement of CD expressions of CD3, CD4 and CD8 as well as NLR might be used as valuable markers for subclinical inflammation in FMF.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis. 2009; 68(2):246â€“248. https://doi.org/10.1136/ard.2008.092031 PMid:18801759

Caliskan M, Gullu H, Yilmaz S, Erdogan D, Unler GK, Ciftci O, et al. Impaired coronary microvascular function in familial Mediterranean fever. Atherosclerosis. 2007; 195(2):e161â€“167. https://doi.org/10.1016/j.atherosclerosis.2007.06.014 PMid:17673217

Onen F. Familial Mediterranean fever. Rheumatol Int. 2006; 26: 489-96. https://doi.org/10.1007/s00296-005-0074-3 PMid:16283319

Medlej-Hashim M, Loiselet J, Lefranc G, MÃ©garbanÃ© A. Familial Mediterranean Fever (FMF): from diagnosis to treatment. Sante. 2004; 14(4): 261-266. PMid:15745878

Zung A, Barash G, Zadik Z, Barash J. Familial Mediterranean fever and growth: effect of disease severity and colchicine treatment. J Pediatr Endocrinol. 2006; 19:15-18. https://doi.org/10.1515/JPEM.2006.19.2.155

Celkan T, Ã‡elik M, KasapÃ§opur Ã–, Ã–zkan A, Apak H, Ocak S, et al. The anemia of familial mediterranean fever disease. J PediatricHematology and Oncology. 2005; 22, 8: 657-665. https://doi.org/10.1080/08880010500278681 PMid:16251171

Korkmaz C, Ozdogan H, Kasapcopur O and Yazici H. Acute phase response in familial Mediterranean fever. Ann Rheum Dis. 2002; 61: 79â€“81. https://doi.org/10.1136/ard.61.1.79 PMid:11779767 PMCid:PMC1753891

Chae JJ, Aksentijevich I, Kastner DL. Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapy. Br J Haematol, 2009; 146: 467-78. https://doi.org/10.1111/j.1365-2141.2009.07733.x PMid:19466978 PMCid:PMC2759843

Gattorno M, La Regina M, Martini A and Manna R. An update on auto-inflammatory diseases.New concepts for new and old diseases. Clin Exp Rheumatol. 2009; 27:354-65. PMid:19473583

Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol, 2009; 27:165â€“97. https://doi.org/10.1146/annurev.immunol.021908.132620 PMid:19302038 PMCid:PMC2734407

YÃ¼ksel S, Ayvazyan L, Gasparyan AY. Familial Mediterranean Fever as an Emerging Clinical Model of Atherogenesis Associated with Low-Grade Inflammation. The Open Cardiovascular Medicine Journal. 2010; 4:51-56. https://doi.org/10.2174/1874192401004010051

Zahorec R. Ratio of neutrophil to lymphocyte countsâ€“rapid and simple parameter of systemic inflammation and stress in critically ill. Bratislavske Lekarske Listy. 2001; 102(1):5-14. PMid:11723675

Uslu AU, Deveci K, Korkmaz S, Aydin B, Senel S, Sancakdar E, Sencan M. Is Neutrophil/ Lymphocyte Ratio Associated with Subclinical Inflammation and Amyloidosis in Patients with Familial Mediterranean Fever? BioMed Research International. 2013;185317:1-5. https://doi.org/10.1155/2013/185317 PMid:23865042 PMCid:PMC3705820

Fonnesu C, Cerquaglia C, Giovinale M, Curigliano V, Verrecchia E, Giuliana de Sicio, et al. Familial Mediterranean Fever: A review for clinical management. J Joint Bone Spine. 2009; 76(3):227-233. https://doi.org/10.1016/j.jbspin.2008.08.004 PMid:19091621

Manna R, Cerquaglia C, Curigliano V, Fonnesu C, Giovinale M, Verrecchia E, et al. Clinical features of familial Mediterranean fever: an Italian overview. Eur Rev Med Pharmacol Sci. 2009; 13(Suppl 1):51â€“53. PMid:19530512

Schroder K, Tschopp J. The inflammasomes. Cell. 2010; 140: 821-832. https://doi.org/10.1016/j.cell.2010.01.040 PMid:20303873

Paust S, Senman B, Von Andrian UH. Adaptive Immune Responses Mediated by Natural Killer Cells. Immunological reviews. 2010; 235(1): 286-296. https://doi.org/10.1111/j.0105-2896.2010.00906.x PMid:20536570 PMCid:PMC2911633

Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or Adaptive Immunity? The Example of Natural Killer Cells. Science. 2011; 331(6013):44-49. https://doi.org/10.1126/science.1198687 PMid:21212348 PMCid:PMC3089969

Jaroszeski M J, Gilbert R, Heller R. Detection and quantitation of cell-cell electrofusion products by flow cytometry. Anal Biochem. 1994; 216:271â€“275. https://doi.org/10.1006/abio.1994.1041 PMid:7513970

Aksu G, Genel F, KoturoÄŸlu G, KurugÃ¶l Z and KÃ¼tÃ¼kÃ§Ã¼ler N. Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr. 2006; 48(1):19-24. PMid:16562781

Wang DQH, Bonfrate L, de Bari O, Wang TY, Portincasa P. Familial Mediterranean Fever: From Pathogenesis to Treatment. J Genet Syndr Gene Ther. 2014; 5:248.

Musabak U, Sengul A, Oktenli C, Pay S, Yesilova Z, Kenar L, et al. Does immune activation continue during an attack-free period in familial Mediterranean fever? Clin Exp Immunol. 2004; 138: 526-533. https://doi.org/10.1111/j.1365-2249.2004.02632.x PMid:15544632 PMCid:PMC1809227

Rimar D, Rosner I, Slobodin G, Boulman N, Toubi E, Kessel A, et al. The Role of Regulatory T Cells in Familial Mediterranean Fever (FMF). Clin Rheumatol. 2012; 31(5):885-8. https://doi.org/10.1007/s10067-011-1935-7 PMid:22234494

Manukyan GP, Ghazaryan KA, KtsoyanZh A, TatyanMV, Khachatryan ZA, Hakobyan GS, et al. Cytokineprofile of Armenian patients with Familial Mediterranean fever. Clin Biochem, 2008; 41:920-2. https://doi.org/10.1016/j.clinbiochem.2008.03.017 PMid:18440310

Erken E, Ozturk OG, Kudas O, Tas DA, Demirtas A, Kibar F, et al. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients. Med Sci Monit. 2015; 21:3547-3554. https://doi.org/10.12659/MSM.895211 PMid:26574972 PMCid:PMC4655612

Schuetz C, Niehues T, Friedrich W, Schwarz K. Autoimmunity, autoinflammation and lymphoma in combined immunodeficiency (CID). Autoimmunity Reviews. 2010; 9:477â€“482. https://doi.org/10.1016/j.autrev.2010.02.005 PMid:20146941

Shanab AM, El-Desouky MA, Kholoussi N, El-Kamah G, Fahmi AA. Evaluation of neopterin as a prognostic factor in patients with beta-thalassemia, in comparison with cytokines and immunoglobulins. Archives of Hellenic Medicine/Arheia Ellenikes Iatrikes. 2015; 32(1).

Livneh A, Drenth JP, Klasen IS, Langevitz P, George J, Shelton DA, et al. Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features. J Rheumatol. 1997; 24:1558-1563. PMid:9263151

Duksal F, Alaygut D, GÃ¼ven AS, Ekici M, Oflaz MB, Tuncer R et al. Neutrophil- lymphocyte ratio in children with familial Mediterranean fever. Eur J Rheumatol. 2015; 1: 20-23. https://doi.org/10.5152/eurjrheumatol.2015.0093 PMid:27708915 PMCid:PMC5047238

Ã–zer S, YÄ±lmaz R, SÃ¶nmezgÃ¶z E, Karaaslan E, TaÅŸkÄ±n S, BÃ¼tÃ¼n Ä°, Demir O. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit. 2015; 23:298-303.

Celikbilek M, Dogan S, Akyol L, Borekci E, Zararsiz G, Kozan M, et al. Neutrophil- Lymphocyte Ratio in Patients With Familial Mediterranean Fever. J Clin Lab Anal. 2015; 29:80-83. https://doi.org/10.1002/jcla.21732 PMid:24687426