Monoclonal Hypergammaglobulinemia Research Articles

Positive anti-nuclear antibody in patients with polyclonal hypergammaglobulinemia suggests the presence of multiple distinct comorbidities.

Objective Polyclonal hypergammaglobulinemia (PHGG) is a classic problem in internal medicine; however, its conditions and diagnostic procedures have not been well studied. We therefore conducted a retrospective study to characterize the PHGG disease spectrum. Methods We included all patients who underwent serum protein electrophoresis (SPEP) at a hematology tertiary referral center during a five-year period. For these patients, globulin clonality was determined and clinical data were extracted from the records. Results Out of 209 consecutive cases of hypergammaglobulinemia demonstrated by SPEP, 79 cases of PHGG were identified. A total of 46 diagnoses were associated with PHGG. Patients with PHGG were younger (median 71.0 years old (yo) vs. 65 years; P = 0.002) and had lower gamma-globulin levels (median, 26.5 g/L vs 24.8 g/L; P = 0.03) than those with monoclonal hypergammaglobulinemia. Interestingly, out of 79 patients with PHGG, 15 were associated with more than one diagnosis, and a female predominance was observed in this specific subset of patients. PHGG cases with multiple diseases showed higher gamma-globulin levels than those with monoclonal hypergammaglobulinemia, in a disease-dependent manner. Additionally, positive antinuclear antibodies (ANAs) had a discriminative ability with an area under the curve of 0.81 (95% confidence interval, 0.65-0.96) and were highly sensitive to multimorbidity in PHGG (sensitivity, 92.3%). Conclusion These results establish a previously underappreciated unique immunological state of multimorbidity in PHGG and indicate that the gamma-globulin levels and ANAs could serve as markers for the clinical assessment of comorbidities in PHGG.

“I Have Macroglobulinemia, and Now What?”—Case Report

Waldenstrom macroglobulinemia (WM) is a chronic, indolent, lymphoproliferative disease of B lymphocytes, characterized by a lymphoplasmocytic lymphoma in the bone marrow and by Immunoglobulin (Ig) M monoclonal hypergammaglobulinemia. WM is considered incurable and the treatment of asymptomatic patients didn’t show benefit in terms of mortality. In this article, the authors present a case report of a 64-years-old woman, without relevant pathological history and asymptomatic, that resorted to a consultation on her Family Health Unit to show the results of a blood analytical study that was requested in a private medical routine consultation. In this study, erythrocyte sedimentation rate (ESR) had a value of 89 mm/h. One month later, ESR remained elevated, 94 mm/h. The further study revealed IgM monoclonal hypergammaglobulinemia of 26 g/L. The patient was sent for additional evaluation in the Haematology Service of the Hospital from the home area. In the course of the study, the patient showed increased anxiety and depressed mood due to the absence of a specific diagnosis. Finally, the diagnosis of WM was established, but, in the absence of symptoms related to the disease, no treatment was offered. The patient remained anxious, depressed and reluctant in accepting the diagnosis of a chronic disease without proper treatment. Therefore, the Family Physician has an essential role not only in choosing the most appropriate complementary diagnostic exams for their patients, but also in dealing with abnormal results of these exams. It’s crucial to protect patients from unnecessary exams or other health interventions. Sometimes, some diseases don’t have a proper treatment, requiring more effort in clarifying and monitoring these cases.

Waldenström's macroglobulinemia - a review

Waldenström's macroglobulinemia (WM) is a lymphoproliferative disease of B lymphocytes, characterized by a lymphoplasmocytic lymphoma in the bone marrow and by IgM monoclonal hypergammaglobulinemia. It was first described in 1944 by Jan Gösta Waldenström, reporting two patients with oronasal bleeding, lymphadenopathy, anemia, thrombocytopenia, high erythrocyte sedimentation rate and serum viscosity, normal radiography and bone marrow infiltrated by lymphoid cells. The WM is a rare disease with a typically indolent clinical course, affecting mainly individuals aged between 63 and 68 years. Most patients have clinical signs and symptoms related to hyperviscosity resulting from IgM monoclonal gammopathy, and/or cytopenias resulting from bone marrow infiltration by lymphoma. The differential diagnosis with other lymphomas is essential for the assessment of prognosis and therapeutic approach. Treatment of patients with asymptomatic WM does not improve the quality of life of patients, or increase their survival, being recommended, therefore, their follow-up. For the treatment of symptomatic patients, alkylating agents, purine analogs and anti-CD20 monoclonal antibodies are used. However, the disease is incurable and the response to therapy is not always favorable. Recent studies have shown promising results with bortezomib, an inhibitor of proteasomes, and some patients respond to thalidomide. In patients with relapse or refractory to therapy, autologous transplantation may be indicated. The aim of this paper is to describe in detail the current knowledge on the pathophysiology of WM, main clinical manifestations, diagnosis, prognosis and treatment.

Quadriparésie hypokaliémique révélant un syndrome de Gougerot-Sjögren associé à une thyroïdite auto-immune

We report a case of 36-year-old woman, admitted for hypotonic tetraparesis. Laboratory tests revealed severe hypokalaemia, acidosis, hyperchloremia and alkaline urinary pH allowing the diagnosis of distal tubular acidosis. Additional investigations led to the diagnosis of primary Sjögren's syndrome associated with Hashimoto's thyroïditis. The evolution was favorable under potassium citrate alkalinisation, the corticosteroid therapy and hormonal substitution. Based on this observation, the pathogenesis of distal tubular acidosis during auto-immune diseases (Sjögren's syndrome, monoclonal hypergammaglobulinemia, hypothyroidism) was discussed as well as its consequences and management.

Histopathologic Features of Multiple Myeloma Involving the Optic Nerves

We report a case of optic nerve involvement by multiple myeloma in which progressive visual loss heralded leukemic transformation and intracranial involvement. Imaging showed enhancing nodules in the intracranial segments of both optic nerves posterior to the optic canals and in the anterior optic tract, optic chiasm, and basal leptomeninges. Postmortem histopathologic examination disclosed malignant plasma cells in the subarachnoid spaces around the optic nerves and in the optic nerves. Infarctions were present in both optic nerves near their junction with the globes. Microscopic examination also showed malignant plasma cell infiltration of the leptomeninges of the cerebrum, brain stem, optic chiasm, pituitary gland, cranial bone marrow, and subarachnoid blood vessels. This is the first reported histopathologic examination in conjunction with MRI of multiple myeloma involving the anterior visual pathway. The mechanism of optic neuropathy in this case is probably related to infiltration of the optic nerve meninges by malignant plasma cells and impaired vascular supply caused by aggregated intraluminal plasma cells and monoclonal hypergammaglobulinemia.

Leucemia de células plasmáticas: variante rara del mieloma múltiple. Caso clínico

Plasma cell leukaemia is a rare variant of multiple myeloma (2-3%), with an aggressive disease with short survival. It is defined as circulating peripheral blood plasma cells exceeding 2.000/ul and 20% of peripheral blood white cells. We present the case of 32-years-old man with left chest-wall pain, hepatomegaly, righ cervical adenopathy, 8800 leukocytes/ul with 33% of lymphocytes and 40% of plasma cell, 10.8 g/dl of proteins and a monoclonal hypergammaglobulinemia. Bone marrow biopsy showed 40-50 % of intramedullary plasma cell. There was a Ig G-kappa paraproteinemia.

Hyperviscosity syndrome in plasma cell dyscrasias.

Hypergammaglobulinemia increases serum viscosity and is the most common cause of hyperviscosity syndrome. Monoclonal hypergammaglobulinemia resulting in hyperviscosity syndrome is seen in multiple myeloma and Waldenström's macroglobulinemia. The reasons for elevated viscosity are increased protein content and large molecular size, abnormal polymerization, and abnormal shape of immunoglobulin molecules. Other hematologic and metabolic abnormalities seen in patients with plasma cell dyscrasias also contribute to hyperviscosity. Symptomatic hyperviscosity is much more common in Waldenström's macroglobulinemia (10 to 30%) than it is in myeloma (2 to 6%). Symptoms of hyperviscosity usually appear when the normal serum viscosity of 1.4 to 1.8 cp reaches 4 to 5 cp, corresponding to a serum immunoglobulin M (IgM) level of at least 3 g/dL, an IgG level of 4 g/dL, and an IgA level of 6 g/dL. Symptoms of hyperviscosity include constitutional symptoms; bleeding; and ocular, neurological, and cardiovascular manifestations. Immediate therapy of symptomatic hyperviscosity is directed at reduction of blood viscosity by plasmapheresis to control symptoms. Long-term management is directed at control of the underlying disease to prevent production of the monoclonal protein. There may be a small proportion of individuals, usually old or with severely compromised performance status, who undergo plasma exchange as the sole symptomatic therapy of hyperviscosity secondary to plasma cell dyscrasia.

Transient Monoclonal Hypergammaglobulinemia during the Course of a Rickettsia Infection

Transient Monoclonal Hypergammaglobulinemia during the Course of a Rickettsia Infection

Biomechanical measurement of skin distensibility in scleredema of Buschke associated with multiple myeloma

We report a case of scleredema of Buschke associated with IgG kappa monoclonal hypergammaglobulinaemia. After myeloma polychemotherapy an improvement in skin involvement was observed and confirmed by means of noninvasive skin elasticity measurements. This suggests a relationship between the two diseases. The bioengineering method used can be useful for early detection and monitoring the skin involvement in patients with this disease association.

Diffuse cutaneous mastocytosis with reactive monoclonal hypergammaglobulinemia

Diffuse cutaneous mastocytosis with reactive monoclonal hypergammaglobulinemia

Plasma cell leukemia with myelofibrosis

We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis improved with combination chemotherapy using vincristine, pirarubicin, and dexamethasone. However, when plasma cell leukemia became resistant to chemotherapies, myelofibrosis also reappeared. This case strongly suggests the pathogenetic relationship between plasma cell leukemia and myelofibrosis.

A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases

We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly, but flared up after several years. Skin lesions appeared in the form of erythema, papules, or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was 0%-2%. The serum lactate dehydrogenase (LDH) value was within normal range and was not associated with hypercalcemia; lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration were very slight. In most cases, hypergammaglobulinemia was seen, and in one case, monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their anti-ATLA antibodies were positive; none had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness and died of cryptococcus meningitis. Based on clinical and pathologic differences, we believe that these cases should be distinguished from typical ATL cases for the purposes of prognosis and treatment.

A Proposal for Smoldering Adult T-Cell Leukemia: A Clinicopathologic Study of Five Cases

We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly, but flared up after several years. Skin lesions appeared in the form of erythema, papules, or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was 0%-2%. The serum lactate dehydrogenase (LDH) value was within normal range and was not associated with hypercalcemia; lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration were very slight. In most cases, hypergammaglobulinemia was seen, and in one case, monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their anti-ATLA antibodies were positive; none had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness and died of cryptococcus meningitis. Based on clinical and pathologic differences, we believe that these cases should be distinguished from typical ATL cases for the purposes of prognosis and treatment.

Enzyme-linked immunosorbent assay (ELISA) for direct quantification of surface-bound platelet immunoglobulins

Surface-bound platelet IgG and IgM were measured by an enzyme-linked immunosorbent assay (ELISA) using washed platelets and commercially available alkaline phosphatase anti-human immunoglobulins (Fc-specific). With this technique platelets from normal donors had small amounts of platelet-bound IgG ranging from 0.00 to 0.16 A405 (absorbance at 405 nm wavelength) (10(7) platelets)-1 (0 to 124 ng) and of platelet-bound IgM ranging from 0.00 to 0.05 A405 (10(7) platelets)-1. Eight out of 10 (80%) thrombocytopenic patients with idiopathic autoimmune thrombocytopenic purpura (IATP) had values of both IgG and IgM exceeding the normal range. In addition, one patient (8%) had platelet-bound IgM only. An inverse relationship was demonstrated in patients with IATP between the blood platelet count and the amount of both IgG and IgM. Increased values were also demonstrated in patients with SLE and patients with monoclonal hypergammaglobulinaemia. The direct ELISA is a useful and reproducible technique for platelet-bound IgG and IgM, which requires standard laboratory equipment only.

Monoclonal hypergammaglobulinemia of the gamma M type in a nine-year-old girl with ataxia-telangiectasia.

A disease pattern in a 9-year-old girl with ataxiatelangiectasia which resembled Aleutian disease of mink of the myeloma-like type is described. During the last three years of life the patient developed an electrophoretic homogeneous γ M peak which probably represented a γ M monoclonal gammopathy. Autopsy disclosed diffuse plasmacytosis of kidney, liver, bone marrow, and lungs, and vascular lesions of the kidneys, spleen, pancreas, and stomach wall. Prior to development of monoclonal gammopathy the patient had a herpes infection. The interrelationship between the thymic hypoplasia, the known high risk for malignancy in these patients, and their susceptibility to viral infections in the pathogenesis of the patent's disease is discussed.

Atypical leukaemia of long duration with monoclonal hypergammaglobulinaemia

A patient with atypical acute leukaemia is described. This patient has, in addition, monoclonal IgG hyperglobulinaemia without myelomatous lesions and is living and well three years after diagnosis. The cell types found in the blood and in the bone marrow are atypical, and the histochemical findings are discussed. The relationship between monoclonal hypergammaglobulinaemia and malignant blood diseases is also discussed, and the literature on the subject reviewed.

Monoclonal and Polyclonal Hypergammaglobulinemia. Clinical and Biological Significance.

Monoclonal and Polyclonal Hypergammaglobulinemia. Clinical and Biological Significance.

ANTICOMPLEMENTARY PHENOMENA IN MONOCLONAL HYPERGLOBULINEMIA.

Abstract Investigations of the mechanism of anticomplementary activity of 5 strongly anticomplementary sera from patients with monoclonal hypergammaglobulinemia have been carried out. Evidence has been presented showing an increased tendency of some gamma myeloma globulins, both in the whole serum and in the isolated state, to become aggregated by heat. The complement inactivation caused by these proteins occurs in a manner identical to that produced by normal gamma globulin or antigen-antibody complexes. Low levels of a normal serum inhibitor of C′ 1 esterase have been found in these strongly anticomplementary sera. The increased capacity to bind complement resulting from the increased aggregation and a decrease in C′ 1 esterase inhibitor level seem to be the inciting factors responsible for the anticomplementary effect seen in gamma myeloma and benign monoclonal hyperglobulinemia.

THE OCCURRENCE OF SEROLOGICAL "ANTIBODY" REAGINS OR SIMILAR GAMMA-GLOBULINS IN CONDITIONS WITH MONOCLONAL HYPERGAMMAGLOBULINEMIA, SUCH AS MYELOMA, MACROGLOBULINEMIA ETC.

Acta Medica ScandinavicaVolume 176, Issue 5 p. 619-631 The Occurrence of Serological “Antibody” Reagins or Similar γ-Globulins in Conditions with Monoclonal Hypergammaglobulinemia, such as Myeloma, Macroglobulinemia etc. JAN WALDENSTRÖM, JAN WALDENSTRÖM Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorSTEN WINBLAD, STEN WINBLAD Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorJAN HÄLLÉN, JAN HÄLLÉN Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorSIGBRITT LIUNGMAN, SIGBRITT LIUNGMAN Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this author JAN WALDENSTRÖM, JAN WALDENSTRÖM Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorSTEN WINBLAD, STEN WINBLAD Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorJAN HÄLLÉN, JAN HÄLLÉN Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this authorSIGBRITT LIUNGMAN, SIGBRITT LIUNGMAN Department of Internal Medicine (Head: J. Waldenström, M. D.) and the Institute of Clinical Bacteriology (Head: S. Winblad, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, SwedenSearch for more papers by this author First published: January/December 1964 https://doi.org/10.1111/j.0954-6820.1964.tb00666.xCitations: 44AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume176, Issue5January/December 1964Pages 619-631 RelatedInformation