T-cell subsets (CD3, CD4, CD8) results were normal; CD19+, 214/µL (normal = 99-566/µL); CD16+CD56+, 63/µL (normal = 79-730/µL). By contrast, common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low serum levels of immunoglobulins (IgG, IgA, and/or IgM) and inability to produce specific protective antibodies in response to infections and immunizations. Myeloma is an accumulation of malfunctioning or \"cancerous\" plasma cells. Besides a defective immune system and susceptibility to infections, CVID is associated with autoimmune disorders, gastrointestinal tract inflammation, granulomatous disease, and malignancies. Each immunoglobulin is made up of two heavy chains and two light chains. Disease monitoring with quantitative serum IgA levels provides a more reliable response assessment in multiple myeloma patients. Multiple myeloma (MM) is a plasma cell malignancy that is recognized for immune system disturbances primarily affecting normal immune globulin (antibody) production with resultant frequent morbidity and mortality. The red arrow in the gamma region of the graph indicates this spike. In fact, because CVID lacks firmly established diagnostic criteria and represents a diagnosis of exclusion,16,17 the coexistence of both conditions is formally disallowed. Additionally, all myeloma cells are identical to each other and produce large quantities of the same specific M protein (for example, IgG or IgA). To check if you have a cancer called multiple myeloma, your doctor may ask you to get a test for M protein.If the substance shows up in your blood or … People who are suffering from diabetes typically have low IgA levels as well. They are used to monitor the disease and its potential complications. Low levels of IgA occur in some types of leukemia, kidney damage (nephrotic syndrome), a problem with the intestines (enteropathy), and a rare inherited disease that affects muscle coordination (ataxia-telangiectasia). The most common type of myeloma is IgG, followed by IgA. !function(d,s,id){var js,fjs=d.getElementsByTagName(s)[0],p=/^http:/.test(d.location)? Cancer is a group of disorders characterized by transformation of normal cells to abnormal cells that grow and multiply uncontrollably. The total serum protein level was 8.9 g/dL (normal = 6.0-7.7 g/dL) with a spike in the g region. Of note, the patient lacked any common risk factors for infectious complications such as renal failure, immunosuppressive therapy, complement deficiency, T-cell abnormalities, or neutropenia. IgE myeloma was first described in 1967 by Johansson and Bennich and till date, only 40 cases have been documented [1] [2] [3]. Although MM and CVID both manifest an abnormal immune system homeostasis, the pathogenesis of the immune defect is distinctly different: Quantitative deficiency of the normal plasma cells in the former and qualitative defect in plasma cell maturation in the latter.Case Presentation: An unusual case of MM associated with profound immunodeficiency mimicking CVID occurred in a 51-year-old man with a history of numerous bacterial infections and low γ-globulin levels.Discussion: A hypothetical connection between MM and CVID is discussed. The next most common is IgA and light chain only. https://doi.org/10.1097/PAS.0b013e3180cab60c. The most commonly reported malignancies are non-Hodgkin lymphomas and gastric cancer, followed by colon cancer, lung cancer, and breast cancer.2,15 A review of the literature revealed 1 case that was identified as myeloma among 117 patients with CVID.15 Although that patient was reported as having myeloma, the disease description with monoclonal IgM; the treatments consisting of plasmapheresis; combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone; and the patient’s death caused by undifferentiated lymphoma were incompatible with the diagnosis. Plasma cells produce antibodies(immunoglobulins) that normally protect us from infection but in multiple myeloma these are nonfunctional and are called paraproteins. Despite the excellent response of the myeloma to therapy, the patient’s deficient immunity failed to recover; therefore, treatment with monthly intravenous immunoglobulin infusions was commenced. As a result, a blood test known as a full blood count is an important part of regular check-ups. But your doctor will want to monitor you very regularly for any symptoms. A value of less than 0.05 was considered significant. Your albumin level is low. Treatment was initiated with lenalidomide, bortezomib, dexamethasone (VRD), and monthly pamidronate infusions. One of the drawbacks of IgA MM diagnostics and monitoring, especially at low IgA levels, is the migration of monoclonal IgA in the β-globulins … Normal values for IgG were 7,02 – 14,6 g/l, for IgA 0,24 – 3,81 g/l, and for IgM 0,54 – 2,27 g/l. The patient’s white blood cell count was 5300/µL (5.3 × 109/L); hemoglobin level, 10.2 g/dL; and platelet count, 429 × 103/µL (429 × 109/L). Some people are born with low or absent levels of IgA antibodies. Eleven months earlier, he was hospitalized for treatment of bacterial meningitis and pneumonia. Simultaneously, the serum protein immunofixation studies revealed the following levels: IgG, 3080 mg/dL (normal = 600-1600 mg/dL); IgA, 12 mg/dL (normal = 40-135 mg/dL); IgM, 16 mg/dL (normal = 30-190 mg/dL); and a monoclonal spike of 2.8 g/dL in the g region. They only produce part of the immunoglobulin called the light chain. Yavorkovsky LL, Hope A. On the other hand, IgM levels in these patients were below, within normal, and above normal values in 94 (88,7 %), 9 (8,5 %), and 3 (2,8 %) patients, respectively. The presentation of MM prompting an immunologist consultation because of recurrent, unusually severe bacterial infections for 10 years preceding the diagnosis was unique for ordinary myeloma. A 51-year-old man was referred to the Immunology Department because of numerous infections escalating in severity in the previous 10 years. The Durie-Salmon system has traditionally been used for the staging of https://doi.org/10.1007/s10875-011-9548-0. Some evidence, however, may call into question the notion that individuals with CVID are naturally protected from the development of MM. Lastly, median IgG in patients with light chain myeloma was 6,3 g/l (range 2,1 – 9,7), median IgA, and median IgM were 0,4 g/l (range 0,1 – 1,7), and 0,3 g/l (range 0,1 – 0,8), respectively. 2 million page views of TPJ articles in PubMed from a broad international readership. Introduction: Multiple myeloma (MM) is a clonal plasma cell disorder commonly associated with secondary immune deficiency. IgE. This is sometimes called smouldering myeloma or indolent myeloma. There are 2 types of light chains - called kappa and lambda. In 106 patients with IgG MM, IgA serum levels were below, within normal, and above normal values in 36 (34 %), 69 (65,1 %), and 1 (0,9 %) patients, respectively. Your B2M is either still normal or a bit high. The immune deficiency in patients with MM is commonly attributed, in addition to the disease, to adverse effects of myeloma treatment. Abundant positively charged M components are produced in multiple myeloma (MM) and the hyponatremia that may accompany it is reported as being a form of pseudohyponatremia . The lack of unambiguous reports of MM in patients with CVID may result from the tremendous diagnostic challenge of identifying both conditions simultaneously, or perhaps the 2 conditions are simply pathogenetically incompatible. The cause of such variation remains largely unknown. Because the patient continued to experience unrelenting, life-threatening infections, supportive treatment with intravenous immunoglobulin infusions was believed necessary. All of the paraproteins from any one individual are DISCUSSION In this study a low level of cobalamin was found in more than one fourth (28%) of the patients with multiple myeloma. The ultimate effect of thi… Table 1 shows a timeline of the case. Accordingly, all immunoglobulin types remained severely depleted (Figure 1). treatment with reduction of the serum IgA level. None of the major registry criteria16,19 attempt to address the complex association of hypogammaglobulinemia/CVID with malignancy because it can be very difficult to determine whether hypogammaglobulinemia/CVID is the cause or the effect of malignancy. IgE myeloma does not present with any specific symptoms or signs when compared to the other forms of multiple myeloma (MM) [4]. The total IgG level was 271 mg/dL; IgG subclass 1 was 202 mg/dL (normal = 382-929 mg/dL), subclass 2 was 44 mg/dL (normal = 241-700 mg/dL), subclass 3 was 6 mg/dL (normal = 22-178 mg/dL), and subclass 4 was 4.4 mg/dL (normal = 4-86 mg/dL). These tests measure levels of blood calcium, total protein, serum beta-2 microglobulin, LDH, C-reactive protein, and blood glucose. Introduction: It is well known that multiple myeloma (MM) is often associated with immunoglobulin (Ig) deficiency and increased risk of infection. Because of the patient’s history of numerous bacterial infections and low g-globulin levels, a diagnosis of CVID was considered highly probable. The patient received another pneumococcal vaccination with a conjugate vaccine (Prevnar13). Likewise, MM manifests considerable variability in the normal immunoglobulin production, with some patients exhibiting profound immunodeficiency and others (15%-30%) maintaining normal or near-normal immunoglobulin concentrations.18 Such a heterogeneity in the presentation of both diseases prompts speculation as to whether their co-occurrence is possible conceptually. Introduction: Multiple myeloma (MM) is a clonal plasma cell disorder commonly associated with secondary immune deficiency. Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit. IgG, IgA, and IgM were below normal values in 8 (72,7 %), 3 (27,3 %), and 9 (81,8 %), respectively. It is usually diagnosed after a routine blood test and does not need treatment straight away. https://doi.org/10.1182/blood-2003-09-3064. As a result they cause a decrease in sodium levels and the anion gap and thus a true hyponatremia. Additionally, despite receiving a pneumococcal vaccine 10 months before his myeloma diagnosis, antibody titers were undetectable. A review of old medical records revealed a low level (< 5%) of monoclonal protein and a g-globulin level of 0.7 g/dL (normal = 0.7-1.7 g/dL) 9 years before presentation. Blood 2004; 104 (11): 4861. doi: https://doi.org/10.1182/blood.V104.11.4861.4861. Indexed in MEDLINE, PubMed Central, EMBASE, EBSCO Academic Search Complete, CrossRef, and SciVerse/Scopus. It is important to point out that no detrimental effects of lenalidomide or bortezomib on humoral immunity have been reported to date.5,6 In fact, the VRD combination that was used in the patient has been associated with a median increase of 81% in uninvolved immunoglobulins after 4 cycles.7, The patient exhibited borderline hypogammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS) 10 years before the myeloma diagnosis. 'http':'https';if(!d.getElementById(id)){js=d.createElement(s);js.id=id;js.src=p+"://platform.twitter.com/widgets.js";fjs.parentNode.insertBefore(js,fjs);}}(document,"script","twitter-wjs"); Leonid L Yavorkovsky, MD, PhD1; Andrew Hope, MD2. Anemia has broad implications. Another study of 36 myeloma patients measured SFLC levels after chemotherapy. The correlation of reduced Ig level to the incidence of infections is being evaluated. Many of the symptoms and complications caused by myeloma are due to changes to the blood, for example anaemia (low red blood cells). The patients with MGUS wer compared to 229 patients with multiple myeloma. First, it serves as a reminder that patients with severe, escalating infections ought to be evaluated earlier for immunodeficiency and, if a diagnosis of immunodeficiency is established, should be monitored for malignancy. In a study with 493 British patients diagnosed with multiple myeloma, the SFLC was evaluated for 17 of these patients and concluded that the SFLC number was more indicative of response to therapy than was the involved immunoglobulin number (such as levels of IgG, IgA, etc). Patients who started with a … Vitamin B12 Level Have Prognostic Significance in Multiple Myeloma Patients? A stain for human herpesvirus 8 was negative. IgM myeloma (IgM MM) is a unique, rare subtype of multiple myeloma (MM) comprising just 0.5 % of all cases of MM. It is hypothesized that MGUS may be associated with an underlying immunodeficiency.9,10 Supporting this hypothesis are the observations of increased risk of infections, including pneumonia and sepsis, in patients with MGUS.9,10 Two cases of monoclonal protein associated with CVID have been reported,8,11 so a coexisting primary immunodeficiency ought to be considered in such cases. Like other types of myeloma with monoclonal gammopathies of other immunoglobulins (e.g., IgG, IgA), patients with IgM MM often have classic symptoms including hypercalcemia, anemia, renal failure, and lytic bone lesions (“CRAB” symptoms). The patient was referred to the oncologist. Conclusion: Most patients with untreated MM have markedly reduced serum Ig levels. Serum protein electrophoresis (SPEP) SPEP checks for the presence of M-protein in the blood. Similarly, IgM level were below, and within normal range in 30 (93,8 %), and 2 (6,3 %) patients with IgA MM. Anemia can be a sign that the myeloma cells are taking up most of your bone marrow and not leaving enough space for your normal marrow cells to make red blood cells. The author(s) have no conflicts of interest to disclose. Lastly, median IgG in patients with light chain myeloma was 6,3 g/l (range 2,1 – 9,7), median IgA, and median IgM were 0,4 g/l (range 0,1 – 1,7), and 0,3 g/l (range 0,1 – 0,8), respectively. The effect of chemotherapy on Ig levels is currently being assessed in our phase III study. lower levels of the other proteins, grouped into areas labeled alpha 1 and 2 ; beta (with two bumps also known as 1 and 2) gamma, which is where the antibody proteins lie on the graph . It’s difficult to diagnose multiple myeloma early. Similarly, IgM level were below, and within normal range in 30 (93,8 %), and 2 (6,3 %) patients with IgA MM. Click here to join the eTOC list or text ETOC to 22828. The net effect is the appearance of large numbers of abnormal cells capable of forming bodily masses, or tumors, with the capacity to advance locally and invade adjacent tissues and organs or spread either through the lymphatics or the blood vessels into distant organs. Clostridium tetani antibody and cytomegalovirus antibodies (immunoglobulin M [IgM] and IgG) were not detectable. The uninvolved IgG subclass levels were reduced in 81% of the IgG1 patients and in all the IgG2, IgG3, and IgG4 patients. MM type was IgG, IgA, light chain, and biclonal in 106 (70,7 %), 32 (21,3 %), 11 (7,5 %), 1 (0,7 %) patients respectively. Although infectious complications are common in MM, most follow the diagnosis of MM and have not been reported during such an extended premyeloma period, to our knowledge.4 Moreover, the number of infections and their burden necessitating frequent hospitalizations were overwhelming by myeloma standards. IgM multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) are two distinct hematologic entities with the common finding of an IgM monoclonal gammopathy. The IgA and IgM levels remained extremely low at 7 mg/dL. The association between CVID and cancer is well established. Because the TACI gene mutation is found in only 10% to 15% of individuals with CVID and may also be found in healthy controls and nonimmunodeficient relatives, it is not considered diagnostic of CVID or predictive of the development of immunodeficiency. About 20 out of 100 people with myeloma (20%) do not produce complete immunoglobulins. Previous article in issue; Next article in issue; Introduction. Burns can also cause an abnormal loss of the proteins … If the IgA blood test results are high, but other immunoglobulin testing results are normal, then this can be an indication that multiple myeloma, leukemia, or lymphoma has developed. Light chain myeloma sometimes called Bence Jones myeloma. Median IgG for IgA MM patients was 3,7 g/l (range 0,1 – 11,8), and median IgM in these 32 patients was 0,2 g/l (range 0 – 1,3). We describe a patient with MM whose distinct clinical presentation and conspicuous laboratory findings were highly suggestive of a concomitant CVID. Tweets by @PermanenteJ to determine if you have low levels of hemoglobin in your blood (a condition called anemia). Six weeks later pneumococcal antibody titers remained undetectable for all tested serotypes. Three months before presentation, he experienced recurrent pneumonia and sepsis. Furthermore, the patient’s pretreatment immune deficiency failed to improve after the otherwise excellent response to the treatment, resulting in undetectable M protein concentrations. Antibodies protect humans from infections. Some people are diagnosed with myeloma that has no symptoms. Our case demonstrates 2 important practical points. At the time, he reported a recent onset of rib and back pain. immunoglobulin!has!overgrowth!that!crowds!out!the!other!types!of!immunoglobulins,!which!is!why!you!may!be!susceptible! The five types of heavy protein chains are G, A, D, E, and M. The two types of light protein chains are kappa (κ) and lambda (λ). These tests are part of a basic medical exam and are also very useful in … Herpes simplex virus type 2 immunoglobulin G (IgG) antibodies were negative. Multiple myeloma has different types and subtypes. Using the principle of electrical neutrality in body … Perm J 2020;24:19.104. https://doi.org/10.1258/shorts.2011.011073. The difficulty of concomitantly identifying the 2 conditions in practice is evident. DOI: https://doi.org/10.7812/TPP/19.104, 1 Department of Oncology, Kaiser Permanente San Jose Medical Center, CA, 2 Department of Immunology, Kaiser Permanente Santa Clara Medical Center, CA, Leonid L Yavorkovsky, MD, PhD (emailProtector.addCloakedMailto("ep_4e582e0a", 0);), Keywords: common variable immunodeficiency, myeloma. Low values. IgG, IgA, and IgM were below normal values in 8 (72,7 %), 3 (27,3 %), and 9 (81,8 %), respectively. The presence of low cobalamin levels was not related to patient characteristics such as sex and age or tumour characteristics such as the type of paraprotein or tumour load. The cause of CVID remains unknown, but mutations in at least 10 genes have been associated with CVID, most commonly the TNFRSF13B (TACI, transmembrane activator and calcium-modulating cyclophilin ligand interactor) gene found in 10% to 15% of individuals with CVID.3. https://doi.org/10.1016/j.jaip.2015.07.025. Because of profoundly low immunoglobulin levels, the usual diagnostic tests to confirm CVID—checking protective antitetanus and antidiphtheria antibody levels before and after booster immunization—were omitted. Furthermore, there are different subtypes of myeloma. Notably, continuous intravenous immunoglobulin infusions were necessary to maintain satisfactory immunoglobulin levels during the following 5 years of treatment, although the patient’s infections were slow to diminish.

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