Immunoglobulin subclass levels in patients with non-Hodgkin lymphoma
Corresponding Author
Robert J. Biggar
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Fax: 45-32-38-31-65.
Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, DenmarkSearch for more papers by this authorMichael Christiansen
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorKlaus Rostgaard
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorKarin Ekström Smedby
Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden
Search for more papers by this authorHans-Olov Adami
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Epidemiology, Harvard School of Public Health and Dana Farber/Harvard Cancer Center, Boston, MA
Search for more papers by this authorBengt Glimelius
Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorHenrik Hjalgrim
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorMads Melbye
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorCorresponding Author
Robert J. Biggar
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Fax: 45-32-38-31-65.
Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, DenmarkSearch for more papers by this authorMichael Christiansen
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorKlaus Rostgaard
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorKarin Ekström Smedby
Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden
Search for more papers by this authorHans-Olov Adami
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Epidemiology, Harvard School of Public Health and Dana Farber/Harvard Cancer Center, Boston, MA
Search for more papers by this authorBengt Glimelius
Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorHenrik Hjalgrim
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorMads Melbye
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Search for more papers by this authorAbstract
Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG4 in 200 NHL patients and 200 age- and sex-matched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10–15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG4 and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL. © 2008 Wiley-Liss, Inc.
References
- 1 Hartge P,Devesa SS,Fraumeni JF,Jr. Hodgkin's and non-Hodgkin's lymphomas. Cancer Surv. 1994; 19/20: 423–53.
- 2 Eltom MA,Jemal A,Mbulaiteye SM,Devesa SS,Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst 2002; 94: 1204–10.
- 3 Sandin S,Hjalgrim H,Glimelius B,Rostgaard K,Pukkala E,Askling J. Incidence of non-Hodgkin's lymphoma in Sweden, Denmark, and Finland from 1960 through 2003: an epidemic that was. Cancer Epidemiol Biomarkers Prev 2006; 15: 1295–300.
- 4 Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299: 1259–60.
- 5 Kinlen L. Immunosuppressive therapy and acquired immunological disorders. Cancer Res 1992; 52 ( Suppl): 5474s–6s.
- 6 Smedby KE,Hjalgrim H,Chang ET,Rostgaard K,Glimelius B,Adami HO,Melbye M. Childhood social environment and risk of non-Hodgkin lymphoma in adults. Cancer Res 2007; 67: 11074–82.
- 7 Rook GA. The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders. Trans R Soc Trop Med Hyg 2007; 101: 1072–4.
- 8 Garn H,Renz H. Epidemiological and immunological evidence for the hygiene hypothesis. Immunobiology 2007; 212: 441–52.
- 9 von Mutius E. Allergies, infections and the hygiene hypothesis–the epidemiological evidence. Immunobiology 2007; 212: 433–9.
- 10 Vercelli D. Mechanisms of the hygiene hypothesis–molecular and otherwise. Curr Opin Immunol 2006; 18: 733–7.
- 11 Schüz J,Morgan G,Böhler E,Kaatsch P,Michaelis J. Atopic disease and childhood acute lymphoblastic leukemia. Int J Cancer 2003; 105: 255–60.
- 12 Wang H,Diepgen TL. Atopic dermatitis and cancer risk. Br J Dermatol 2006; 154: 205–10.
- 13 Eriksson NE,Mikoczy Z,Hagmar L. Cancer incidence in 13811 patients skin tested for allergy. J Investig Allergol Clin Immunol 2005; 15: 161–6.
- 14 Merrill RM,Isakson RT,Beck RE. The association between allergies and cancer: what is currently known? Ann Allergy Asthma Immunol 2007; 99: 102–16.
- 15 Grulich AE,Vajdic CM,Cozen W. Altered immunity as a risk factor for non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 2007; 16: 405–8.
- 16 Cozen W,Cerhan JR,Martinez-Maza O,Ward MH,Linet M,Colt JS,Davis S,Severson RK,Hartge P,Bernstein L. The effect of atopy, childhood crowding, and other immune-related factors on non-Hodgkin lymphoma risk. Cancer Causes Control 2007; 18: 821–31.
- 17 Melbye M,Smedby KE,Lehtinen T,Rostgaard K,Glimelius B,Munksgaard L,Schöllkopf C,Sundström C,Chang ET,Koskela P,Adami HO,Hjalgrim H. Atopy and risk of non-Hodgkin lymphoma. J Natl Cancer Inst 2007; 99: 158–66.
- 18 Eckschlager T,Průsa R,Hladíková M,Radvanská J,Slabý K,Radvanský J. Lymphocyte subpopulations and immunoglobulin levels in Hodgkin's disease survivors. Neoplasma 2004; 51: 261–4.
- 19 Wang H,Rothenbacher D,Löw M,Stegmaier C,Brenner H,Diepgen TL. Atopic diseases, immunoglobulin E and risk of cancer of the prostate, breast, lung and colorectum. Int J Cancer 2006; 119: 695–701.
- 20 Ellison-Loschmann L,Benavente Y,Douwes J,Buendia E,Font R,Alvaro T,Kogevinas M,de Sanjosé S. Immunoglobulin E levels and risk of lymphoma in a case-control study in Spain. Cancer Epidemiol Biomarkers Prev 2007; 16: 1492–8.
- 21 Grulich AE,Vajdic CM,Riminton S,Hughes AM,Kricker A,Armstrong BK. Re: atopy and risk of non-Hodgkin lymphoma. J Natl Cancer Inst 2007; 99: 1417.
- 22 Lindelöf B,Granath F,Tengvall-Linder M,Ekbom A. Allergy and cancer. Allergy 2005; 60: 1116–20.
- 23 Mardia KV,Kent JT,Bibby JM. Multivariate analysis. London: Academic Press, 1979.
- 24 Gribben JG,Cardoso AA,Schultze JL,Nadler LM. Biologic response modifiers in acute lymphoblastic leukemia. Leukemia 1997; 11 ( Suppl 4): S31–3.
- 25 Thebeau LG,Morrison LA. Mechanism of reduced T-cell effector functions and class-switched antibody responses to herpes simplex virus type 2 in the absence of B7 costimulation. J Virol 2003; 77: 2426–35.
- 26 Suvas S,Singh V,Sahdev S,Vohra H,Agrewala JN. Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. J Biol Chem 2002; 277: 7766–75.
- 27 Hock BD,Starling GC,Patton WN,Salm N,Bond K,McArthur LT,McKenzie JL. Identification of a circulating soluble form of CD80: levels in patients with hematological malignancies. Leuk Lymphoma 2004; 45: 2111–8.
- 28 Ranheim EA,Cantwell MJ,Kipps TJ. Expression of CD27 and its ligand. CD70, on chronic lymphocytic leukemia B cells. Blood 1995; 85: 3556–65.