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REVIEW PAPER
HELLP syndrome: a complication or a new autoimmune syndrome?
 
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Online publication date: 2014-11-30
 
 
Reumatologia 2014;52(6):377-383
 
KEYWORDS
ABSTRACT
The HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a pregnancy-specific disease characterized by hemolysis with elevated lactate dehydrogenase, elevated liver enzymes, and decreased platelet count. It is considered a severe variant of the hypertensive disorders that occur during pregnancy together with the pre-eclampsia (PE) and the eclampsia giving symptoms in the mother from 20 weeks’ gestation onward. All these conditions are multi-system pregnancy-related diseases associated with an increase in blood pressure and in both the perinatal and the maternal morbidity/mortality. Observational studies suggest that steroid treatment in HELLP syndrome may improve the hematological and biochemical features in the mother and the perinatal outcome. The present review aims to show that the HELLP syndrome may be considered as an autoimmune disorder itself. Biomarkers of the immune system can be a useful tool improving the diagnostic and therapeutic management of women with HELLP by delineating the underlying etiology of this syndrome.
 
REFERENCES (48)
1.
Cunningham FG, Leveno KJ, Bloom SL, et al. Pregnancy hypertension. In: Williams Obstetrics. Cunningham FG, Leveno KJ, Bloom SL, et al. (eds.). 23rd ed. McGraw Hill; USA 2009. .
 
2.
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376: 631-644. .
 
3.
Pedersen M, Stayner L, Slama R, et al. Ambient air pollution and pregnancy-induced hypertensive disorders: a systematic review and meta-analysis. Hypertension 2014; 64: 494-500. .
 
4.
Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996; 175: 460-464. .
 
5.
Abildgaard U, Heimdal K. Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review. Eur J Obstet Gynecol Reprod Biol 2013; 166: 117-123. .
 
6.
Denney JM, Nelson EL, Wadhwa PD, et al. Longitudinal modulation of immune system cytokine profile during pregnancy. Cytokine 2010; 53: 170-177. .
 
7.
Shaarawy M, Nagui AR. Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion. Acta Obstet Gynecol Scand 1997; 76: 205-211. .
 
8.
Calleja-Agius J, Muttukrishna S, Jauniaux E. The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome. Int J Interferon Cytokine Mediator Res 2012; 4: 1-15. .
 
9.
Wallace K, Morris R, Kyle PB, et al. Hypertension, inflammation and T lymphocytes are increased in a rat model of HELLP syndrome. Hypertens Pregnancy 2014; 33: 41-54. .
 
10.
Corradetti A, Saccucci F, Emanuelli M, et al. The role of p38alpha mitogen-activated protein kinase gene in the HELLP syndrome. Cell Stress Chaperones 2010; 15: 95-100. .
 
11.
Adams RH, Porras A, Alonso G, et al. Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development. Mol Cell 2000; 6: 109-116. .
 
12.
Molvarec A, Tamási L, Losonczy G, et al. Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell Stress Chaperones 2010; 15: 237-247. .
 
13.
Molvarec A, Rigo J Jr, Nagy B, et al. Serum heat shock protein 70 levels are decreased in normal human pregnancy. J Reprod Immunol 2007; 74: 163-169. .
 
14.
Pockley AG. Heat shock proteins as regulators of the immune response. Lancet 2003; 362: 469-476. .
 
15.
Madach K, Molvarec A, Rigo J Jr, et al. Elevated serum 70 kDa heat shock protein level reflects tissue damage and disease severity in the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Eur J Obstet Gynecol Reprod Biol 2008; 139: 133-138. .
 
16.
Asea A, Kraeft SK, Kurt-Jones EA, et al. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 2000; 6: 435-442. .
 
17.
Prohaszka Z, Singh M, Nagy K, et al. Heat shock protein 70 is a potent activator of the human complement system. Cell Stress Chaperones 2002; 7: 17-22. .
 
18.
Perricone C, De Carolis C, Perricone R. Glutathione: a key player in autoimmunity. Autoimmun Rev 2009; 8: 697-701. .
 
19.
Perricone C, De Carolis C, Giacomelli R, et al. Inhibition of the complement system by glutathione: molecular mechanisms and potential therapeutic implications. Int J Immunopathol Pharmacol 2011; 24: 63-68. .
 
20.
Knapen MF, Mulder TP, Van Rooij IA, et al. Low whole blood glutathione levels in pregnancies complicated by preeclampsia or the hemolysis, elevated liver enzymes, low platelets syndrome. Obstet Gynecol 1998; 92: 1012-1015. .
 
21.
Chimenti MS, Ballanti E, Triggianese P, Perricone R. Vasculitides and the Complement System: a Comprehensive Review. Clin Rev Allergy Immunol 2014; doi 10.1007/s12016-014-8453-8. .
 
22.
Girardi G, Yarilin D, Thurman JM, et al. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 2006; 203: 2165-2175. .
 
23.
Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta 2013; 34: 201-203. .
 
24.
Perricone C, De Carolis C, Perricone R. Pregnancy and autoimmunity: a common problem. Best Pract Res Clin Rheumatol 2012; 26: 47-60. .
 
25.
Perricone R, De Carolis C, Perricone C, Shoenfeld Y. NK cells in autoimmunity: a two-edg’d weapon of the immune system. Autoimmun Rev 2008; 7: 384-390. .
 
26.
Konova E. The role of NK cells in the autoimmune thyroid disease-associated pregnancy loss. Clinic Rev Allergy Immunol 2010; 39: 176-184. .
 
27.
Borzychowski AM, Croy BA, Chan WL, et al. Changes in systemic type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by natural killer cells. Eur J Immunol 2005; 35: 3054-3063. .
 
28.
Colonna M, Jonjic S, Watzl C. Natural killer cells: fighting viruses and much more. Nat Immunol 2011; 12: 107-110. .
 
29.
Riederer I, Sievert W, Eissner G, et al. Irradiation-induced up-regulation of HLA-E on macrovascular endothelial cells confers protection against killing by activated natural killer cells. PLoS ONE 2010; 5: 15339. .
 
30.
Bueno-Sánchez JC, Agudelo-Jaramillo B, Escobar-Aguilerae LF, et al. Cytokine production by non-stimulated peripheral blood NK cells and lymphocytes in early-onset severe pre-eclampsia without HELLP. J Reprod Immunol 2013; 97: 223-231. .
 
31.
Perricone C, De Carolis C, Giacomelli R, et al. High levels of NK cells in the peripheral blood of patients affected with anti-phospholipid syndrome and recurrent spontaneous abortion: a potential new hypothesis. Rheumatology 2007; 46: 1574-1578. .
 
32.
Perricone R, Di Muzio G, Perricone C, et al. High levels of peripheral blood NK cells in women suffering from recurrent spontaneous abortion are reverted from high-dose intravenous immunoglobulins. Am J Reprod Immunol 2006; 55: 232-239. .
 
33.
Seshadri S, Sunkara SK. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update 2014; 20: 429-438. .
 
34.
Triggianese P, Perricone C, Perricone R, De Carolis C. Prolactin and Natural Killer Cells: Evaluating the Neuroendocrine-immune Axis in Women with Primary Infertility and Recurrent Spontaneous Abortion. Am J Reprod Immunol 2014; doi:10.1111/aji.12335. .
 
35.
Scholz C, Toth B, Santoso L, et al. Distribution and maturity of dendritic cells in diseases of insufficient placentation. Am J Reprod Immunol 2008; 60: 238-245 . .
 
36.
van Dijk M, Oudejans C. (Epi)genetics of pregnancy-associated diseases. Front Genet 2013; 4: 180. .
 
37.
Robillard PY, Dekker G, Chaouat G, Hulsey TC. Etiology of preeclampsia: maternal vascular predisposition and couple disease – mutual exclusion or complementarity? J Reprod Immunol 2007; 76: 1-7. .
 
38.
Reyes LM, García RG, Ruiz SL, et al. Angiogenic imbalance and plasma lipid alterations in women with preeclampsia from a developing country. Growth Factors 2012; 30: 158-166. .
 
39.
Wortelboer EJ, Koster MP, Cuckle HS, et al. First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia. BJOG 2010; 117: 1384-1389. .
 
40.
Bussen S, Bussen D. Influence of the vascular endothelial growth factor on the development of severe pre-eclampsia or HELLP syndrome. Arch Gynecol Obstet 2011; 284: 551-557. .
 
41.
Visser S, Hermes W, Ket JC, et al. Systematic review and metaanalysis on nonclassic cardiovascular biomarkers after hypertensive pregnancy disorders. Am J Obstet Gynecol 2014; 211: 373.e1-373.e9. .
 
42.
Wolfberg AJ, Lee-Parritz A, Peller AJ, Lieberman ES. Association of rheumatologic disease with preeclampsia. Obstet Gynecol 2004; 103: 1190-1193. .
 
43.
Appenzeller S, Souza FH, Wagner Silva de Souza A, et al. HELLP syndrome and its relationship with antiphospholipid syndrome and antiphospholipid antibodies. Semin Arthritis Rheum 2011; 41: 517-523. .
 
44.
Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun 2014; 48-49: 20-25. .
 
45.
Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A Review. BMC Pregnancy Childbirth 2009; 9: 8. .
 
46.
Martin JN Jr, Rinehart BK, May WL, et al. The spectrum of severe preeclampsia: comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification. Am J Obstet Gynecol 1999; 180: 1373-1384. .
 
47.
Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy. Cochrane Database Syst Rev 2010; 9: CD008148. .
 
48.
Wallace K, Martin JN Jr, Tam Tam K, et al. Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study. Am J Obstet Gynecol 2013; 208: 380.e1-380.e8.
 
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