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Elevated serum gamma globulins in apparently healthy Nigerians living in Ogbomoso: a possible manifestation of phagocytic dysfunction

Publication: LymphoSign Journal
27 August 2021

Abstract

Background: Serum protein abnormalities, particularly elevated gamma globulins (hypergammaglobulinemia, HGG), have been reported in apparently healthy Nigerians living in Ogbomoso and elsewhere. Since the mechanisms for this phenomenon have not been fully substantiated, we hypothesized that impaired neutrophil phagocytosis could contribute to this condition.
Methods: Healthy humans exhibiting HGG were identified using serum protein electrophoresis performed on cellulose acetate gel in barbital buffer (pH 8.6). GelQuant image analysis and quantitation software were further employed to quantify the gamma globulin fraction. Neutrophils were isolated from K3EDTA anticoagulated peripheral blood using Histopaque neutrophil isolation reagent. Neutrophil phagocytic activity was analyzed using a non-subjective commercial colorimetric phagocytosis assay kit.
Results: The purity and viability of isolated neutrophils were approximately 94% and 92%, respectively. Ex-vivo phagocytic activity of neutrophils isolated from apparently healthy subjects exhibiting HGG, expressed as a percentage of the average absorbance of the control group, was 48.1 ± 8.6% which was significantly lower (p < 0.05) compared to the controls (98.9 ± 14.3%).
Conclusion: Since neutrophils play crucial roles in innate immune responses, impairment of neutrophil phagocytic activity may lead to persistent antigenic stimulations of the adaptive immune system. This could in turn orchestrate gamma globulins expression leading to HGG.
Statement of novelty: We demonstrated reduced neutrophil phagocytic activity as a possible basis for hypergammaglobulinemia in healthy Nigerians, perhaps for the first time.

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REFERENCES

Adedeji A.L., Adenikinju R.O., Ajele J.O., and Olawoye T.L. 2014. Serum protein electrophoresis under effective control of HIV-1 disease progression. EXCLI J. 13: 761–771.
Adedeji A.L., Faniran O.G., and Olawoye T.L. 2015. Immunologic characteristics of apparently healthy Nigerians exhibiting abnormal SPE: A preliminary study. RRJoI. 5(3): 1–6.
Baranov M.V., Revelo N.H., Dingjan I., Maraspini R., Ter Beest M., Honigmann A., and van den Bogaart G. 2016. SWAP70 organizes the actin cytoskeleton and is essential for phagocytosis. Cell Rep. 17(6): 1518–1531.
Buadi F., Hsing A.W., Katzmann J.A., Pfeiffer R.M., Waxman A., Yeboah E.D., Biritwum R.B., Tettey Y., Adjei A., Chu L.W., DeMarzo A., Netto G.J., Dispenzieri A., Kyle R.A., Rajkumar S.V., and Landgren O. 2011. High prevalence of polyclonal hypergamma-globulinemia in adult males in Ghana, Africa. Am. J. Hematol. 86(7): 554–558.
Burtis, C.A., and Ashwood, E.R. 1999. Tietz textbook of clinical chemistry. Philadelphia.
Carneiro V.M.A., Bezerra A.C.B., Guimarães M.D.C.M., and Muniz-Junqueira M.I. 2012. Decreased phagocytic function in neutrophils and monocytes from peripheral blood in periodontal disease. J. Appl. Oral. Sci. 20(5): 503–509.
Conley M.E., Notarangelo L.D., and Etzioni A. 1999. Diagnostic criteria for primary immunodeficiencies. Clin. Immunol. 93(3): 190–197.
Dantas E.O., Aranda C.S., Rêgo Silva A.M., Tavares F.S., Severo Ferreira J.F., de Quadros Coelho M.A., de Siqueira Kovalhuk L.C., Roxo Júnior P., Toledo E.C., Porto Neto A.C., de Sousa Vieira H.M., Takano O.A., Nobre F.A., Sano F., Nudelman V., de Farias Sales V.S., Silva Segundo G.R., Villar Guedes H.T., Félix E., Marques S.M., and Costa Carvalho B.T. 2015. Doctors’ awareness concerning primary immunodeficiencies in Brazil. AllergolImmunopathol. 43(3): 272–278.
Doumas B.T., Watson W.A., and Biggs H.G. 1971. Albumin standards and the measurement of serum albumin with bromocreasol green. Clin. Chim. Acta. 31(1): 87–96.
Engelich G., Wright D.G., and Hartshorn K.L. 2001. Acquired disorders of phagocyte function complicating medical and surgical illnesses. Clin. Infect. Dis. 33(12): 2040–2048.
Fallatah H.I. and Akbar H.O. 2010. Elevated serum immunoglobulin G levels in patients with chronic liver disease in comparison to patients with autoimmune hepatitis. Libyan. J. Med. 5.
Freitas M., Porto G., Lima J.L., and Fernandes E. 2008. Isolation and activation of human neutrophils in vitro. The importance of the anticoagulant used during blood collection. Clin. Biochem. 41(7–8): 570–575.
Gideon H.P., Phuah J., Junecko B.A., and Mattila J.T. 2019. Neutrophils express pro- and anti-inflammatory cytokines in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques. Mucosal. Immunol. 12(6): 1370–1381.
Joshi M.B., Ahamed R., Hegde M., Nair A.S., Ramachandra L., and Satyamoorthy K. 2020. Glucose induces metabolic reprogramming in neutrophils during type 2 diabetes to form constitutive extracellular traps and decreased responsiveness to lipopolysaccharides. BiochimBiophys. Acta Mol. Basis Dis. 1866(12): 165940.
Katzmann J.A., Clark R., Wiegert E., Sanders E., Oda R.P., Kyle R.A., Namyst-Goldberg C., and Landers J.P. 1997. Identification of monoclonal proteins in serum: a quantitative comparison of acetate, agarose gel, and capillary electrophoresis. Electrophoresis, 18(10): 1775–1780.
Kekow J., Hobusch G., and Gross W.L. 1988. Predominance of the IgG1 subclass in the hypergammaglobulinemia observed in pre-AIDS and AIDS. Cancer Detect Prev. 12(1–6): 211–216.
Khakabimamaghani S., Najafi A., Ranjbar R., and Raam M. 2013. GelClust: a software tool for gel electrophoresis images analysis and dendrogram generation. Comput Methods Programs Biomed. 111(2): 512–518.
Kumar V. 2020. Phagocytosis: Phenotypically simple yet a mechanistically complex process. Int. Rev. Immunol. 39(3): 118–150.
Kutscher S., Dembek C.J., Deckert S., Russo C., Körber N., Bogner J.R., Geisler F., Umgelter A., Neuenhahn M., Albrecht J., Cosma A., Protzer U., and Bauer T. 2013. Overnight resting of PBMC changes functional signatures of antigen specific T- cell responses: impact for immune monitoring within clinical trials. PLoS ONE, 8(10): e76215.
Leach J., Morton J.P., and Sansom O.J. 2019. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Mol. Immunol. 110: 69–76.
Lehman H.K. and Segal B.H. 2020. The role of neutrophils in host defense and disease. J. Allergy Clin. Immunol. 145(6): 1535–1544.
Ley K., Hoffman H.M., Kubes P., Cassatella M.A., Zychlinsky A., Hedrick C.C., and Catz S.D. 2018. Neutrophils: New insights and open questions. Sci. Immunol. 3(30): eaat4579.
Liew P.X. and Kubes P. 2019. The Neutrophil’s Role During Health and Disease. Physiol. Rev. 99(2): 1223–1248.
Lo M.S., Zurakowski D., Son M.B., and Sundel R.P. 2013. Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: A retrospective cohort study. Pediatr. Rheumatol. Online J. 11(1): 42.
Mancini G., Carbonara A.O., and Heremans J.F. 1965. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry, 2(3): 235–254.
May R.C. and Machesky L.M. 2001. Phagocytosis and the actin cytoskeleton. J. Cell Sci. 114(Pt 6): 1061–1077.
Mazzachi B.C., Peake M.J., and Ehrhardt V. 2000. Reference range and method comparison studies for enzymatic and Jaffé creatinine assays in plasma and serum and early morning urine. Clin. Lab. 46(1–2): 53–55.
Nordenfelt P. and Tapper H. 2011. Phagosome dynamics during phagocytosis by neutrophils. J. Leukoc. Biol. 90(2): 271–284.
Oh H., Siano B., and Diamond S. 2008. Neutrophil isolation protocol. J. Vis. Exp. 23(17): 745.
Papayannopoulos V. 2018. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 18(2): 134–147.
Pimenta F., Palma S., Constantino-Silva R.N., and Grumach A.S. 2019. Hypogammaglobulinemia: a diagnosis that must not be overlooked. Braz. J. Med. Biol. Res. 52(10): e8926.
Plummer, D.T. 1978. An introduction to practical biochemistry, 3rd ed. McGraw - Hill book company, Maidenhead.
Quast I., Peschke B., and Lünemann J.D. 2017. Regulation of antibody effector functions through IgG Fc N-glycosylation. Cell Mol. Life Sci. 74(5): 837–847.
Reitman S. and Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am. J. Clin. Pathol. 28(1): 56–63.
Riggione O., Stokes R.P., and Thompson R.A. 1983. Predominance of IgG3 subclass in primary cirrhosis. Br. Med. J. 286(6370): 1015–1016.
Rosales C. 2020. Neutrophils at the crossroads of innate and adaptive immunity. J. Leukoc. Biol. 108(1): 377–396.
Rosales C. and Uribe-Querol E. 2017. Phagocytosis: A Fundamental Process in Immunity. Biomed. Res. Int. 2017: 9042851.
Schofield F.D. 1957. The serum protein pattern of West Africans in Britain. Trans. R. Soc. Trop. Med. Hyg. 51(4): 332–337.
Silvestre-Roig C., Fridlender Z.G., Glogauer M., and Scapini P. 2019. Neutrophil diversity in health and disease. Trends Immunol. 40(7): 565–583.
Tamassia N., Bianchetto-Aguilera F., Arruda-Silva F., Gardiman E., Gasperini S., Calzetti F., and Cassatella M.A. 2018. Cytokine production by human neutrophils: Revisiting the “dark side of the moon”. Eur. J. Clin. Invest. 48(Suppl 2): e12952.
Teng T.S., Ji A.L., Ji X.Y., and Li Y.Z. 2017. Neutrophils and immunity: From bactericidal action to being conquered. J. Immunol. Res. 2017: 9671604.
Upton J. 2014. Immunodeficiencies with hypergammaglobulinemia: A review. LymphoSign Journal, 2(2): 57–73.
Weichselbaum T.E. 1946. An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma. Am. J. Clin. Pathol. 10: 40–49.
Yousif A.M., Ablhad N.S., and Ismail P.A. 2018. Serum immunofixation electrophoresis as a diagnostic method for monoclonal gammopathies in patients with multiple myeloma. Al-Mustansiriyah J. Sci. 29(4).

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Information & Authors

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Published In

cover image LymphoSign Journal
LymphoSign Journal
Volume 8Number 3September 2021
Pages: 86 - 93

History

Received: 14 August 2021
Accepted: 25 August 2021
Accepted manuscript online: 27 August 2021

Authors

Affiliations

Adebayo Lawrence Adedeji
Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
Dauda Jimoh
Nigerian Navy School of Health Sciences, Offa, Nigeria
Jelili Abiodun Badmus
Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
Ibrahim Olabanji Bello
Nigerian Navy School of Health Sciences, Offa, Nigeria
Ibrahim Eleha Suleiman
Department of Chemical Pathology, University of Ilorin, Ilorin, Nigeria
Olubunmi Gloria Ayelagbe [email protected]
Department of Chemical Pathology, Ladoke Akintola University, Ogbomoso, Nigeria

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