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Review

The impact of individual clinical features in cold agglutinin disease: hemolytic versus non-hemolytic symptoms

, , , &
Pages 479-492 | Received 05 Mar 2024, Accepted 21 Jun 2024, Published online: 28 Jun 2024

References

  • Schubothe H. The cold hemagglutinin disease. Semin Hematol. 1966;3(1):27–47.
  • Berentsen S, Barcellini W, D’Sa S, et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood. 2020;136(4):480–488. doi: 10.1182/blood.2020005674
  • Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013;122(7):1114–1121. doi: 10.1182/blood-2013-02-474437
  • Ulvestad E, Berentsen S, Bø K, et al. Clinical immunology of chronic cold agglutinin disease. Eur J Haematol. 1999;63(4):259–266. doi: 10.1111/j.1600-0609.1999.tb01887.x
  • Randen U, Trøen G, Tierens A, et al. Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma. Haematologica. 2014;99(3):497–504. doi: 10.3324/haematol.2013.091702
  • Naresh KN, Rossi D, Chen X, et al. Cold agglutinin disease. In: WHO classification of haematolymphoid tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2022. p. 349. Available from: https://tumourclassification.iarc.who.int/chaptercontent/363/349
  • Guenther A, Tierens A, Malecka A, et al. The histopathology of cold agglutinin disease-associated B-Cell lymphoproliferative disease. Am J Clin Pathol. 2023;160(3):229–237. doi: 10.1093/ajcp/aqad048
  • Winter O, Dame C, Jundt F, et al. Pathogenic long-lived plasma cells and their survival niches in autoimmunity, malignancy, and allergy. J Immunol. 2012;189(11):5105–5111. doi: 10.4049/jimmunol.1202317
  • Jonsen J, Kåss E. Investigations on complement and complement components in a case of high-titer cold hemagglutination. Acta Med Scand. 1959;165(3):229–233. doi: 10.1111/j.0954-6820.1959.tb14494.x
  • Berentsen S, D’Sa S, Randen U, et al. Cold agglutinin disease: Improved understanding of pathogenesis helps define targets for therapy. Hemato. 2022;3(1):574–594. doi: 10.3390/hemato3040040
  • Hill QA, Hill A, Berentsen S. Defining autoimmune hemolytic anemia: a systematic review of the terminology used for diagnosis and treatment. Blood Adv. 2019;3(12):1897–1906. doi: 10.1182/bloodadvances.2019000036
  • Jäger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the first international consensus meeting. Blood Rev. 2020;41(1):100648. doi: 10.1016/j.blre.2019.100648
  • Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26(3):107–115. doi: 10.1016/j.blre.2012.01.002
  • Zagorski E, Pawar T, Rahimian S, et al. Cold agglutinin autoimmune haemolytic anaemia associated with novel coronavirus (COVID-19). Br J Haematol. 2020;190(4):e183–e184. doi: 10.1111/bjh.16892
  • Crisp D, Pruzanski W. B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med. 1982;72(6):915–922. doi: 10.1016/0002-9343(82)90852-x
  • Berentsen S. Cold agglutinin disease. Hematology Am Soc Hematol Educ Program. 2016;2016(1):226–231. doi: 10.1182/asheducation-2016.1.226
  • Hansen DL, Berentsen S, Fattizzo B, et al. Seasonal variation in the incidence of cold agglutinin disease in Norway, Denmark, and Italy. Am J Hematol. 2021;96(7):E262–E265. doi: 10.1002/ajh.26196
  • Berentsen S, Ulvestad E, Langholm R, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica. 2006;91(4):460–466.
  • Berentsen S. How I treat cold agglutinin disease. Blood. 2021;137(10):1295–1303. doi: 10.1182/blood.2019003809
  • Berentsen S, Fattizzo B, Barcellini W. The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket? Front Immunol. 2023;14:1180509. doi: 10.3389/fimmu.2023.1180509
  • Gelbenegger G, Berentsen S, Jilma B. Monoclonal antibodies for treatment of cold agglutinin disease. Expert Opin Biol Ther. 2023;23(5):395–406. doi: 10.1080/14712598.2023.2209265
  • Berentsen S, Barcellini W, Longo DL. Autoimmune Hemolytic Anemias. N Engl J Med. 2021;385(15):1407–1419. doi: 10.1056/NEJMra2033982
  • Gertz MA. Updates on the diagnosis and management of cold autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2022;36(2):341–352. doi: 10.1016/j.hoc.2021.11.001
  • Christenson WN, Dacie JV, Croucher BE, et al. Electrophoretic studies on sera containing high-titre cold haemagglutinins: identification of the antibody as the cause of an abnormal γ Peak. Br J Haematol. 1957;3(3):262–273. doi: 10.1111/j.1365-2141.1957.tb05795.x
  • Harboe M, van Furth R, Schubothe H, et al. Exclusive occurrence of K chains in isolated cold haemagglutinins. Scand J Haematol. 1965;2(3):259–266. doi: 10.1111/j.1600-0609.1965.tb01303.x
  • Berentsen S, Bø K, Shammas FV, et al. Chronic cold agglutinin disease of the “idiopathic” type is a premalignant or low-grade malignant lymphoproliferative disease. APMIS. 1997;105(5):354–362. doi: 10.1111/j.1699-0463.1997.tb00581.x
  • Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720–1748. doi: 10.1038/s41375-022-01620-2
  • Berentsen S, Röth A, Randen U, et al. Cold agglutinin disease: current challenges and further prospects. J Blood Med. 2019;10:93–103. doi: 10.2147/JBM.S177621
  • Dacie J. Auto-immune haemolytic anaemia (AIHA): cold-antibody syndromes II: immunochemistry and specificity of the antibodies; serum complement in autoimmune haemolytic anaemia. In: Dacie J, editor. The haemolytic anaemias. Vol. 3. London: Churchill Livingstone; 1992. p. 240–295.
  • Arthold C, Skrabs C, Mitterbauer-Hohendanner G, et al. Cold antibody autoimmune hemolytic anemia and lymphoproliferative disorders: a retrospective study of 20 patients including clinical, hematological, and molecular findings. Wien Klin Wochenschr. 2014;126(11–12):376–382. doi: 10.1007/s00508-014-0547-z
  • Malecka A, Trøen G, Tierens A, et al. Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity. Haematologica. 2016;101(9):e361–e364. doi: 10.3324/haematol.2016.146126
  • Khwaja J, D’Sa S, Minnema MC, et al. IgM monoclonal gammopathies of clinical significance: diagnosis and management. Haematologica. 2022;107(9):2037–2050. doi: 10.3324/haematol.2022.280953
  • Malecka A, Trøen G, Delabie J, et al. The mutational landscape of cold agglutinin disease: CARD11 and CXCR4 mutations are correlated with lower hemoglobin levels. Am J Hematol. 2021;96(8):E279–E283. doi: 10.1002/ajh.26205
  • Malecka A, Trøen G, Tierens A, et al. Frequent somatic mutations of KMT2D (MLL2) and CARD11 genes in primary cold agglutinin disease. Br J Haematol. 2018;183(5):838–842. doi: 10.1111/bjh.15063
  • Malecka A, Delabie J, Østlie I, et al. Cold agglutinin–associated B-cell lymphoproliferative disease shows highly recurrent gains of chromosome 3 and 12 or 18. Blood Adv. 2020;4(6):993–996. doi: 10.1182/bloodadvances.2020001608
  • Malecka A, Østlie I, Trøen G, et al. Gene expression analysis revealed downregulation of complement receptor 1 in clonal B cells in cold agglutinin disease. Clinical And Experimental Immunology. 2023; online ahead of print. 216(1):45–54. doi: 10.1093/cei/uxad135
  • Issitt PD. I blood group system and its relationship to disease. J Med Lab Technol. 1968;25(1):1–6.
  • Marsh WL. Anti-i: a cold antibody defining the Ii relationship in human red cells. Br J Haematol. 1961;7(1):200–209. doi: 10.1111/j.1365-2141.1961.tb00329.x
  • Berentsen S. New insights in the pathogenesis and therapy of cold agglutinin-mediated autoimmune hemolytic anemia. Front Immunol. 2020;11:590. doi: 10.3389/fimmu.2020.00590
  • Rosse WF, Adams JP. The variability of hemolysis in the cold agglutinin syndrome. Blood. 1980;56(3):409–416. doi: 10.1182/blood.V56.3.409.409
  • Silberstein LE, Berkman EM, Schreiber AD. Cold hemagglutinin disease associated with IgG cold-reactive antibody. Ann Intern Med. 1987;106(2):238–242. doi: 10.7326/0003-4819-106-2-238
  • Pascual V, Victor K, Spellerberg M, et al. VH restriction among human cold agglutinins. The VH4-21 gene segment is required to encode anti-I and anti-i specificities. J Immunol. 1992;149(7):2337–2344. doi: 10.4049/jimmunol.149.7.2337
  • Potter KN, Hobby P, Klijn S, et al. Evidence for involvement of a hydrophobic patch in framework region 1 of human V4-34-encoded igs in recognition of the red blood cell I antigen. J Immunol. 2002;169(7):3777–3782. doi: 10.4049/jimmunol.169.7.3777
  • Li Y, Spellerberg MB, Stevenson FK, et al. The I binding specificity of human VH 4-34 (VH 4-21) encoded antibodies is determined by both VH framework region 1 and complementarity determining region 3. J Mol Biol. 1996;256(3):577–589. doi: 10.1006/jmbi.1996.0110
  • Paliwal S, Thakkar D, Chin WJ, et al. Selective targeting of pathogenic auto-reactive VH4–34 B cells with a rationally developed anti-VH4–34 antibody offers a new therapeutic approach for autoimmune disorders. J Immunol. 2023;210(1_Supplement):.238.20–.238.20. doi: 10.4049/jimmunol.210.Supp.238.20
  • Pascual V, Capra JD. VH4-21, a human VH gene segment overrepresented in the autoimmune repertoire. Arthritis Rheum. 1992;35(1):11–18. doi: 10.1002/art.1780350103
  • Kraj P, Friedman DF, Stevenson F, et al. Evidence for the overexpression of the VH4-34 (VH4.21) ig gene segment in the normal adult human peripheral blood B cell repertoire. J Immunol. 1995;154(12):6406–6420. doi: 10.4049/jimmunol.154.12.6406
  • Jain MD, Cabrerizo-Sanchez R, Karkouti K, et al. Seek and you shall find–but then what do you do? Cold agglutinins in cardiopulmonary bypass and a single-center experience with cold agglutinin screening before cardiac surgery. Transfus Med Rev. 2013;27(2):65–73. doi: 10.1016/j.tmrv.2012.12.001
  • Stone MJ, McElroy YG, Pestronk A, et al. Human monoclonal macroglobulins with antibody activity. Seminars In Oncology. 2003;30(2):318–324. doi: 10.1053/sonc.2003.50077
  • Jefferies LC, Carchidi CM, Silberstein LE. Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment. J Clin Invest. 1993;92(6):2821–2833. doi: 10.1172/JCI116902
  • Potter KN. Molecular characterization of cold agglutinins. Transfus Sci. 2000;22(1–2):113–119. doi: 10.1016/s0955-3886(00)00031-x
  • Pugh-Bernard AE, Silverman GJ, Cappione AJ, et al. Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest. 2001;108(7):1061–1070. doi: 10.1172/JCI200112462
  • Jaffe CJ, Atkinson JP, Frank MM. The role of complement in the clearance of cold agglutinin-sensitized erythrocytes in man. J Clin Invest. 1976;58(4):942–949. doi: 10.1172/JCI108547
  • Heni M, Saur SJ. Blood clotting at room temperature in cold agglutinin disease. Blood. 2013;121(25):4975. doi: 10.1182/blood-2012-12-472324
  • Solanki DL, Blackburn BC. Spurious red blood cell parameters due to serum cold agglutinins: observations on Ortho ELT-8 cell counter. Am J Clin Pathol. 1985;83(2):218–222. doi: 10.1093/ajcp/83.2.218
  • Petrusic V, Zivkovic I, Stojanovic M, et al. Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers. Immunol Res. 2011;51(1):97–107. doi: 10.1007/s12026-011-8236-8
  • Petrusic V, Zivkovic I, Stojanovic M, et al. Hexameric immunoglobulin M in humans: desired or unwanted? Med Hypotheses. 2011;77(6):959–961. doi: 10.1016/j.mehy.2011.08.018
  • Hughey CT, Brewer JW, Colosia AD, et al. Production of IgM hexamers by normal and autoimmune B cells: implications for the physiologic role of hexameric IgM. J Immunol. 1998;161(8):4091–4097. doi: 10.4049/jimmunol.161.8.4091
  • Pruzanski W, Faird N, Keystone E, et al. The influence of homogeneous cold agglutinins on polymorphonuclear and mononuclear phagocytes. Clin Immunol Immunopathol. 1975;4(2):277–285. doi: 10.1016/0090-1229(75)90063-X
  • Dunstan RA, Simpson MB, Rosse WF. The presence of the Ii blood group system on human platelets. Am J Clin Pathol. 1984;82(1):74–77. doi: 10.1093/ajcp/82.1.74
  • Lee JH. Neutrophil aggregation on the peripheral blood smear in a patient with cold agglutinin disease. Ann Hematol. 2017;96(5):885–886. doi: 10.1007/s00277-017-2962-5
  • Berentsen S. Neutrophil aggregation on the peripheral blood smear in a patient with cold agglutinin disease. Ann Hematol. 2017;96(10):1767–1768. doi: 10.1007/s00277-017-3077-8
  • Gavriilaki E, Brodsky RA. Complementopathies and precision medicine. J Clin Invest. 2020;130(5):2152–2163. doi: 10.1172/JCI136094
  • Berentsen S, Hill A, Hill QA, et al. Novel insights into the treatment of complement-mediated hemolytic anemias. Ther Adv Hematol. 2019;10:2040620719873321. doi: 10.1177/2040620719873321
  • Shi J, Rose EL, Singh A, et al. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood. 2014;123(26):4015–4022. doi: 10.1182/blood-2014-02-556027
  • Berentsen S, Randen U, Tjønnfjord GE. Cold agglutinin-mediated autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2015;29(3):455–471. doi: 10.1016/j.hoc.2015.01.002
  • Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. Semin Hematol. 2018;55(3):141–149. doi: 10.1053/j.seminhematol.2018.04.002
  • Varela JC, Tomlinson S. Complement: an overview for the clinician. Hematol Oncol Clin North Am. 2015;29(3):409–427. doi: 10.1016/j.hoc.2015.02.001
  • Ulvestad E, Berentsen S, Mollnes TE. Acute phase haemolysis in chronic cold agglutinin disease. Scand J Immunol. 2001;54(1–2):239–242. doi: 10.1046/j.1365-3083.2001.00960.x
  • Mold C, Gewurz H, Du Clos TW. Regulation of complement activation by C-reactive protein. Immunopharmacology. 1999;42(1–3):23–30. doi: 10.1016/s0162-3109(99)00007-7
  • Ahearn JM, Fearon DT. Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv Immunol. 1989;46:183–219. doi: 10.1016/s0065-2776(08)60654-9
  • Iida K, Nussenzweig V. Functional properties of membrane-associated complement receptor CR1. J Immunol. 1983;130(4):1876–1880. doi: 10.4049/jimmunol.130.4.1876
  • Kremlitzka M, Polgar A, Fulop L, et al. Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis patients. Int Immunol. 2013;25(1):25–33. doi: 10.1093/intimm/dxs090
  • Erdei A, Kovacs KG, Nagy-Balo Z, et al. New aspects in the regulation of human B cell functions by complement receptors CR1, CR2, CR3 and CR4. Immunol Lett. 2021;237:42–57. doi: 10.1016/j.imlet.2021.06.006
  • Broome CM, Cunningham JM, Mullins M, et al. Increased risk of thrombotic events in cold agglutinin disease: a 10-year retrospective analysis. Res Pract Thromb Haemost. 2020;4(4):628–635. doi: 10.1002/rth2.12333
  • Joly F, Schmitt LA, Watson PAM, et al. The burden of cold agglutinin disease on patients’ daily life: web-based cross-sectional survey of 50 American patients. JMIR Form Res. 2022;6(7):e34248. doi: 10.2196/34248
  • Rørvik K. The syndrome of high-titre cold haemagglutination; a survey and a case report. Acta Med Scand. 1954;148(4):299–308. doi: 10.1111/j.0954-6820.1954.tb01722.x
  • U.S. Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) version 4.0. 2009. Available from: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
  • Berentsen S, Randen U, Oksman M, et al. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017;130(4):537–541. doi: 10.1182/blood-2017-04-778175
  • Tomkins O, Berentsen S, Arulogun S, et al. Daratumumab for disabling cold agglutinin disease refractory to B-cell directed therapy. Am J Hematol. 2020;95(10):E293–E295. doi: 10.1002/ajh.25932
  • Khwaja J, Vos JMI, Pluimers TE, et al. Clinical and clonal characteristics of monoclonal immunoglobulin M-associated type I cryoglobulinaemia. Br J Haematol. 2024;204(1):177–185. doi: 10.1111/bjh.19112
  • Khwaja J, Japzon N, Gabriel M, et al. Cold agglutinin disease and cryoglobulinaemia: a frequent coexistence with clinical impact. Br J Haematol. 2023; online ahead of print.204(2). doi: 10.1111/bjh.19185
  • Lai JS, Beaumont JL, Ogale S, et al. Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol. 2011;38(4):672–679. doi: 10.3899/jrheum.100799
  • Röth A, Barcellini W, S D, et al. Sutimlimab in cold agglutinin disease. N Engl J Med. 2021;384(14):1323–1334. doi: 10.1056/NEJMoa2027760
  • Röth A, Berentsen S, Barcellini W, et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022;140(9):980–991. doi: 10.1182/blood.2021014955
  • Ulvestad E. Paradoxical haemolysis in a patient with cold agglutinin disease. Eur J Haematol. 1998;60(2):93–100. doi: 10.1111/j.1600-0609.1998.tb01004.x
  • Tjønnfjord E, Vengen OA, Berentsen S, et al. Prophylactic use of eculizumab during surgery in chronic cold agglutinin disease. BMJ Case Rep. 2017 May 9;2017:bcr2016219066. doi: 10.1136/bcr-2016-219066
  • Tvedt THA, Steien E, Øvrebø B, et al. Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery. American J Hematol. 2022;97(2):E51–E54. doi: 10.1002/ajh.26409
  • Perez-Lamas L, Moreno-Jimenez G, Tenorio-Nunez MC, et al. Hemolytic crisis due to covid-19 vaccination in a woman with cold agglutinin disease. Am J Hematol. 2021;96(8):E288–E291. doi: 10.1002/ajh.26214
  • Lyckholm LJ, Edmond MB, Eagle K. Images in clinical medicine. Seasonal hemolysis due to cold-agglutinin syndrome. N Engl J Med. 1996;334(7):437. doi: 10.1056/NEJM199602153340705
  • Fattizzo B, Bortolotti M, Giannotta JA, et al. Intravascular hemolysis and multitreatment predict thrombosis in patients with autoimmune hemolytic anemia. J Thromb Haemost. 2022;20(8):1852–1858. doi: 10.1111/jth.15757
  • Röth A, Bommer M, Hüttmann A, et al. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018;2(19):2543–2549. doi: 10.1182/bloodadvances.2018024190
  • Kamesaki T, Nishimura JI, Wada H, et al. Demographic characteristics, thromboembolism risk, and treatment patterns for patients with cold agglutinin disease in Japan. Int J Hematol. 2020;112(3):307–315. doi: 10.1007/s12185-020-02899-6
  • Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121(25):4985–4996; quiz 5105. doi: 10.1182/blood-2012-09-311381
  • Heurich M, McCluskey G. Complement and coagulation crosstalk - factor H in the spotlight. Immunobiology. 2023;228(6):152707. doi: 10.1016/j.imbio.2023.152707
  • Audia S, Bach B, Samson M, et al. Venous thromboembolic events during warm autoimmune hemolytic anemia. PLoS One. 2018;13(11):e0207218. doi: 10.1371/journal.pone.0207218
  • Berentsen S. How I manage patients with cold agglutinin disease. Br J Haematol. 2018;181(3):320–330. doi: 10.1111/bjh.15109
  • Berentsen S, Tjønnfjord GE. Current treatment options in cold agglutinin disease: B-cell directed or complement directed therapy? Transfus Med Rev. 2022;36(4):36(181–187. doi: 10.1016/j.tmrv.2022.05.001
  • Berentsen S, Ulvestad E, Gjertsen BT, et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004;103(8):2925–2928. doi: 10.1182/blood-2003-10-3597
  • Schöllkopf C, Kjeldsen L, Bjerrum OW, et al. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma. 2006;47(2):253–260. doi: 10.1080/10428190500286481
  • Berentsen S, Randen U, Vågan AM, et al. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010;116(17):3180–3184. doi: 10.1182/blood-2010-06-288647
  • Rossi G, Gramegna D, Paoloni F, et al. Short course of bortezomib in anemic patients with relapsed cold agglutinin disease: a phase 2 prospective GIMEMA study. Blood. 2018;132(5):547–550. doi: 10.1182/blood-2018-03-835413
  • Jalink M, Berentsen S, Castillo JJ, et al. Effect of ibrutinib treatment on hemolytic anemia and acrocyanosis in cold agglutinin disease/cold agglutinin syndrome. Blood. 2021;138(20):2002–2005. doi: 10.1182/blood.2021012039
  • Jalink M, Jacobs CF, Khwaja J, et al. Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease. Blood Adv. 2024; Online ahaed of print.8(11):2622–2634. doi: 10.1182/bloodadvances.2024012585
  • Tenny S, Varacello M. Evidence based medicine. NIH: National Library of Medicine; 2022; [cited 2024 Apr 13]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470182/
  • Fadlallah J, Michel M, Crickx E, et al. Bortezomib and dexamethasone, an original approach for treating multi-refractory warm autoimmune haemolytic anaemia. Br J Haematol. 2019;187(1):124–128. doi: 10.1111/bjh.16009
  • Yao M, Zhang J, Li Y, et al. Combination of low-dose rituximab, bortezomib and dexamethasone for the treatment of autoimmune hemolytic anemia. Medicine (Baltimore). 2022;101(4):e28679. doi: 10.1097/MD.0000000000028679
  • El-Ayoubi A, Wang JQ, Hein N, et al. Role of plasma cells in waldenstrom macroglobulinaemia. Pathology. 2017;49(4):337–345. doi: 10.1016/j.pathol.2017.02.004
  • Del Giudice I, Matutes E, Osuji N, et al. Delayed response to fludarabine in lymphoplasmacytic lymphoma/waldenström’s macroglobulinemia. Haematologica. 2005;90(2):268–270.
  • Berentsen S, Barcellini W, D’Sa S, et al. Sutimlimab for treatment of cold agglutinin disease: why, how and for whom? Immunotherapy. 2022;14(15):1191–1204. doi: 10.2217/imt-2022-0085
  • Bartko J, Schörgenhofer C, Schwameis M, et al. A randomized, first-in-human, healthy volunteer trial of sutimlimab, a humanized antibody for the specific inhibition of the classical complement pathway. Clin Pharmacol Ther. 2018;104(4):655–663. doi: 10.1002/cpt.1111
  • Jäger U, D’Sa S, Schörgenhofer C, et al. Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial. Blood. 2019;133(9):893–901. doi: 10.1182/blood-2018-06-856930
  • Gelbenegger G, Jaeger U, Fillitz M, et al. Sustained sutimlimab response for 3 years in patients with cold agglutinin disease: a phase I, open-label, extension trial. Br J Haematol. 2022;198(4). doi: 10.1111/bjh.18289
  • Röth A, Barcellini W, S D, et al. Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease. Am J Hematol. 2023;98(8):1246–1253. doi: 10.1002/ajh.26965
  • Gelbenegger G, Jager U, Fillitz M, et al. Sustained hematologic remission after discontinuation of sutimlimab treatment in patients with cold agglutinin disease. Blood Adv. 2023;7(10):1987–1990. doi: 10.1182/bloodadvances.2022008574
  • Datta SS, Berentsen S. Management of autoimmune haemolytic anaemia in low-to-middle income countries: current challenges and the way forward. Lancet Reg Health Southeast Asia. 2024;23(4):100343. doi: 10.1016/j.lansea.2023.100343
  • Gertz M, Roman E, Fattizzo B, et al. Inhibition of C3 with APL-2 ControlsHaemolysis and increases haemoglobin levels in subjects with autoimmune haemolytic anaemia (AIHA). Hemasphere. 2019;3(Supplement 1):405. doi: 10.1097/01.HS9.0000561876.96057.48
  • Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384(11):1028–1037. doi: 10.1056/NEJMoa2029073
  • Zaninoni A, Giannotta J, Galli A, et al. The immunomodulatory effect and clinical efficacy of daratumumab in a patient with cold agglutinin disease. Front Immunol. 2021;12. doi: 10.3389/fimmu.2021.649441
  • Mackness BC, Jaworski JA, Boudanova E, et al. Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life. MAbs. 2019;11(7):1276–1288. doi: 10.1080/19420862.2019.1633883
  • Simmons KT, Chan J, Hussain S, et al. Anti-C1s humanized monoclonal antibody SAR445088: a classical pathway complement inhibitor specific for the active form of C1s. Clin Immunol. 2023;251(109629):109629. doi: 10.1016/j.clim.2023.109629
  • D’Sa SP, Vos JMI, Barcellini W, et al. Safety, tolerability and activity of the active C1s antibody riliprubart in cold agglutinin disease: a Phase 1b study. Blood. 2023;143(8):713–720. doi: 10.1182/blood.2023022153
  • Lansita JA, Mease KM, Qiu H, et al. Nonclinical development of ANX005: a humanized anti-C1q antibody for treatment of autoimmune and neurodegenerative diseases. Int J Toxicol. 2017;36(6):449–462. doi: 10.1177/1091581817740873
  • Gertz MA, Qiu H, Kendall L, et al. ANX005, an inhibitory antibody against C1q, blocks complement activation triggered by cold agglutinins in human disease. 58th meeting of the american society of hematology, San Diego, CA, USA. Blood. 2016;128:1265. doi: 10.1182/blood.V128.22.1265.1265
  • Van de Walle I, Silence K, Budding K, et al. ARGX-117, a therapeutic complement inhibiting antibody targeting C2. J Allergy Clin Immunol. 2021;147(4):1420–1429 e1427. doi: 10.1016/j.jaci.2020.08.028
  • Hummingbird-Bioscience. Hummingbird bioscience to present preclinical proof of concept for potentially first-in-class antibody targeting autoimmune diseases. [cited 2024 Feb 8]. Available from: https://www.prnewswire.com/news-releases/hummingbird-bioscience-to-present-preclinical-proof-of-concept-for-potentially-first-in-class-antibody-targeting-autoimmune-diseases-301817891.html.2023
  • Evans LS, Lewis KE, DeMonte D, et al. Povetacicept, an enhanced dual APRIL/BAFF Antagonist that modulates b lymphocytes and pathogenic autoantibodies for the treatment of lupus and other B cell-related autoimmune diseases. Arthritis Rheumatol. 2023;75(7):1187–1202. doi: 10.1002/art.42462
  • Samy E, Wax S, Huard B, et al. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Int Rev Immunol. 2017;36(1):3–19. doi: 10.1080/08830185.2016.1276903
  • Broome C, Kuter DJ, McCrae KR, et al. Initial report of povetacicept, an enhanced dual BAFF/APRIL antagonist, in autoimmune cytopenias: the RUBY-4 study. Blood. 2023;142(Supplement 1):5520. doi: 10.1182/blood-2023-179305
  • Berentsen S. Cold agglutinins: fending off the attack. Blood. 2019;133(9):885–886. doi: 10.1182/blood-2019-01-894303
  • Grillo-Lopez AJ, White CA, Varns C, et al. Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Semin Oncol. 1999;26(5 Suppl 14):66–73.
  • Das SS, Das S, Shastry S, et al. Real-world data from India on clinical practices in the management of autoimmune haemolytic anaemia: a survey-based cross-sectional assessment. Transfus Clin Biol. 2023;30(1):137–142. doi: 10.1016/j.tracli.2022.09.069
  • Mulder FVM, Evers D, de Haas M, et al. Severe autoimmune hemolytic anemia; epidemiology, clinical management, outcomes and knowledge gaps. Front Immunol. 2023;14(1228142). doi: 10.3389/fimmu.2023.1228142

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