Crioproteinemia: nuove frontiere per i clinici e il laboratorio
Cryoproteinemia: new frontiers for clinicians and the laboratory

AUTORI

ABSTRACT

Cryoproteinemia: new frontiers for clinicians and the laboratory

Cryoproteinaemia is characterised by the presence of detectable proteins in both serum and plasma that precipitate at 4°C and dissolve at 37°C. Cryoglobulins are constituted by immunoglobulins and are detectable in both serum and plasma, whereas cryofibrinogen is detectable only in plasma. The importance of studying cryoproteinemia was the main theme of the meeting held in Modena in March 2023, entitled: Cryoglobulinemia. Laboratory and clinic, a fruitful collaboration for the correct management of a rare pathology – 4th edition, organised by the Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC) and the Italian Association for the fight against Cryoglobulinaemia (ALCRI). The aim of this conference is to promote a dialogue between clinicians and laboratory professionals, highlighting the information that the clinician expects from the laboratory and the critical points that the laboratory faces when performing a test that is still predominantly performed manually. During the meeting, data from three laboratories were presented and compared, and a group of clinicians who deal with cryoproteinemia in different medical fields – rheumatologists, nephrologists, haematologists, and neurologists – contributed their experience in treating patients with cryoproteinemia. The collaboration between laboratory and clinic and the respective scientific societies (SIBioC and ALCRI) have made possible to draw a common line to guide both entities in their daily activity. The road seems long and complex, but a common system is emerging from this interaction, the fruits from which patient will benefit.

BIBLIOGRAFIA

BIBLIOGRAFIA
1. Natali P, Debbia D, Cucinelli MR, Trenti T, Amati G, Spinella A et al. Analysis of cryoproteins with a focus on cryofibrinogen: a study on 103 patients. Chin Chem Lab Med 2022;60:1796-803.
2. Desbois AC, Cacoub P, Saadoun D. Cryoglobulinemia: an update in 2019. Joint Bone Spine 2019;86:707-13.
3. Blain H, Cacoub P, Musset L, Costedoat-Chalumeau N, Silberstein C, Chosidow O et al. Cryofibrinogenaemia: a study of 49 patients. Clin Exp Immunol 2000;120:253-60.
4. Mariscal-Rodríguez A, Villar Guimerans LM, López-Trascasa M, González MH, Naranjo EM. Laboratory guidelines for the diagnosis of patients with cryoglobulinaemic syndrome. Rev Clin Esp 2019;219:505-13.
5. Michaud M, Pourrat J. Cryofibrinogenemia. J Clin Rheumatol 2013;19:142-8.
6. Natali P, Debbia D, Turra F, Savoia M, Farci Santarcangeli D, Cigliana G et al. Indagine sulle modalità operative dell’analisi delle crioproteine: dalla fase preanalitica alla refertazione. Biochim Clin 2023;47:158-70.
7. Basile U, Gulli F, Gragnani L, Fognani E, Napodano C, Pocino K et al. IgG3 subclass: a possible trigger of mixed cryoglobulin cascade in hepatitis C virus chronic infection. Dig Liver Dis 2017;49:1233-9.
8. Napodano C, Gulli F, Rapaccini GL, Marino M, Basile U. Cryoglobulins: identification, classification, and novel biomarkers of mysterious proteins. Adv Clin Chem 2021;104:299-340.
9. Korst DR, Kratochvil CH. “Cryofibrinogen” in a case of lung neoplasm associated with thrombophlebitis migrans. Blood 1955;10:945-53.
10. Moiseev S, Luqmani R, Novikov P, Shevtsova T. Cryofibrinogenaemia. A neglected disease. Rheumatology (Oxford) 2017;56:1445-51.
11. Gómez-Fernández C, López-Sundh AE, González-Vela C, Ocejo-Vinyals JG, Mayor-Ibarguren A, Salas-Venero CA et al. High prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 outbreak. Int J Dermatol 2020;59:1475-84.
12. De Vita S, Quartuccio L, Isola M, Mazzaro C, Scaini P, Lenzi M et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 2012;64:843-53.
13. Delluc A, Saadoun D, Ghillani-Dalbin P, Sene D, Piette JC, Cacoub P. Cryofibrinogen in patients with hepatitis C virus infection. Am J Med 2008;121:624-31.
14. Soyfoo MS, Goubella A, Cogan E, Wautrecht JC, Ocmant A, Stordeur P. Clinical significance of cryofibrinogenemia: Possible pathophysiological link with Raynaud’s phenomenon. J Rheumatol 2012;39:119-24.
15. Belizna C, Loufrani L, Subra JF, Godin M, Jolly P, Vitecocq O et al. A 5-year prospective follow-up study in essential cryofibrinogenemia patients. Autoimmun Rev 2011;10:559-62.
16. Saadoun D, Elalamy I, Ghillani-Dalbin P, Sene D, Delluc A, Cacoub P et al. Cryofibrinogenemia: new insights into clinical and pathogenic features. Am J Med 2009;122:1128-35.
17. Belizna CC, Tron F, Joly P, Godin M, Hamidou M, Lévesque H. Outcome of essential cryofibrinogenaemia in a series of 61 patients. Rheumatology (Oxford) 2008;47:205-7.
18. Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J Invest Dermatol 2017;137:e11-6.
19. Hachulla E, Launay D. Diagnosis and classification of systemic sclerosis. Allergy Immunol 2011;40:78-83.
20. Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017;76:1327-39.
21. Barrett M, Prendiville J, Pardy B, Cream JJ. Cryofibrinogenaemia and acute gangrene in systemic sclerosis. Postgrad Med J 1986;62:935-6.
22. Van Den Hoogen F, Khanna D, Fransen J, Baron M, Tyndall A, Matucci-Cerinic M et al. 2013 classification criteria for systemic sclerosis: An american college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737-47.
23. Humbert M, Kovacs G, Hoeper M, Berger RMF, Brida M, Carlsen J et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022;38:3618-731.
24. Sudo M, Sakamaki Y, Hosojima M, Yamamoto S, Ito Y, Imai N et al. Cryofibrinogen-associated glomerulonephritis diagnosed by mass spectrometry and immunoelectron microscopy. Hum Pathol Case Rep 2019;15:83-7.
25. Sethi S, Yachoui R, Murray DL, Radhakrishnan J, Alexander MP. Cryofibrinogen-associated glomerulonephritis. Am J Kidney Dis 2017;69:302-8.
26. Terrier B, Izzedine H, Musset L, Ghillani P, Deray G, Saadoun D et al. Prevalence and clinical significance of cryofibrinogenaemia in patients with renal disorders. Nephrol Dial Transplant 2011:26:3577-81.
27. Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biological and clinical significance of cryoglobulins. Am J Med 1974;57:775-88.
28. Kolopp-Sarda M, Miossec P. Pratical details for detection and interpretation of cryoglobulins. Clin Chem 2022;68:282-90.
29. Podell D, Packman C, Maniloff J, Abraham G. Characterization of monoclonal IgG cryoglobulins: fine-structural and morphological analysis. Blood 1987;69:677-81.
30. Néel A, Perrin F, Decaux O, Dejoie T, Tessoulin B, Halliez M et al. Long-term outcome of monoclonal (type 1) cryoglobulinemia. Am J Hematol 2014;89:156-61.
31. Kolopp-Sarda MN, Nombel A, Miossec P. Cryoglobulins today: detection and immunologic characteristics of 1,675 positive samples from 13,439 patients obtained over six years. Arthritis Rheumatol 2019;71:1904-12.
32. Muchtar E, Magen H, Gertz MA. How I treat cryoglobulinemia. Blood 2017;129:289-98.
33. Payet J, Livartowski J, Kavian N, Chandesris O, Dupin N, Wallet N et al. Type I cryoglobulinemia in multiple myeloma, a rare entity: Analysis of clinical and biological characteristics of seven cases and review of the literature. Leuk Lymphoma 2013;54:767-77.
34. Castillo JJ, Garcia-Sanz R, Hatjiharissi E, Kyle RA, Leleu X, McMaster M et al. Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinemia: a task force from the 8th International Workshop on Waldenström Macroglobulinemia. Br J Haematol 2016;175:77-86.
35. Biasiotta A, Casato M, La Cesa S, Colantuono S, Di Stefano G, Leone C et al. Clinical, neurophysiological, and skin biopsy findings in peripheral neuropathy associated with hepatitis C virus-related cryoglobulinemia. J Neurol 2014;261:725-31.
36. Feldman L, Dhamne M, Li Y. Neurologic manifestations associated with cryoglobulinemia: a single center experience. J Neurol Sci 2019;398:121-7.
37. Callaghan BC, Price RS, Chen KS, Feldman EL. The importance of rare subtypes in diagnosis and treatment of peripheral neuropathy: a review. JAMA Neurol 2015;72:1510-8.
38. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA et al. Evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review). Muscle Nerve 2009;39:116-25.
39. Scarpato S, Galassi G, Monti G, Mazzaro C, Mascia MT, Scaini P et al. Peripheral neuropathy in mixed cryoglobulinaemia: clinical assessment and therapeutic approach. Clin Exp Rheumatol 2020;38:1231-7.