Hypergammaglobulinemia Research Articles

Understanding hypergammaglobulinemia in experimental or natural visceral leishmaniasis.

Nonspecific hypergammaglobulinemia (HGG) occurs in symptomatic human visceral leishmaniasis (VL) caused by L. L. infantum. This study assessed this finding in experimental infection in hamsters and natural infection in dogs. The serum concentration of proteins, albumin and globulins was determined through the biuret and bromocresol green reaction, where the HGG was better expressed through the albumin/globulin (A/G) ratio. HGG was associated with a higher concentration of specific anti-glycan antibodies (BSA-G)/promastigote soluble extract (PSE) and the presence of circulating immune complexes (IC) by dissociative enzyme-linked immunoassay (ELISA). The study found monovalent IC in 37.9% (PSE) and 50% (BSA-G) of sera from infected hamsters, with increased frequency as the disease progressed. HGG was found in >60% of the samples in dogs with VL, associated with higher levels of specific immunoglobulin (Ig)A and IgM, but not IgG, determined using the PSE and BSA-G ELISA. HGG was associated with the presence of monovalent IC in 58.9% (PSE) and 63.4% (BSA-G) positive dog samples. HGG may result not only from the nonspecific activation of B cells, with greater production of specific and nonspecific antibodies, but also due to lower IgG excretion due to the presence of soluble monovalent IC. HGG correlates to the progression of VL and may be a marker for manifested disease.

Case Report: Case report: An unusual presentation of granulomatosis with polyangiitis

Aim: We are reporting a case of an unusual presentation of granulomatosis with polyangiitis (GPA) with liver involvement. Case presentation: A 45-year-old male patient presented with erythematous plaques on the face and bilateral nasal obstruction. On physical examination, the patient had a ring-shaped squamous plaque on the face. The laboratory findings revealed an accelerated erythrocyte sedimentation rate at 100 mm/h, an elevated C-reactive protein at 66 mg/L, hyper gamma globulinemia 16 g/L and an elevated alkaline phosphatase (twice the upper normal limit). The craniofacial and thoracoabdominal computed tomography (CT) -scans showed ethmoid and maxillary sinusitis, low facial bone density, multiple mediastinal and hilar lymphadenopathy, diffuse small pulmonary nodules, and hepatomegaly. A cutaneous lesion biopsy, the nasal mucosa, and the liver showed a chronic inflammatory granulomatosis process with necrosis. Serum anti-neutrophil cytoplasmic antibody (ANCA) against PR3 was positive. The clinical, biological, radiological, and histological findings substantiated the diagnosis of GPA. The patient received systemic steroids combined with cyclophosphamide pulses on days 1, 14 and 28 and then he was lost to follow-up. Two-years later, he presented with a cardiac failure and skin ulcer in the right lower limb. A nasal endoscopic exam showed nasal septum cartilage perforation with resorption of the middle and inferior nasal concha. Two weeks later, he developed a diffuse alveolar hemorrhage and was therefore transferred to the intensive care unit but died of respiratory failure 3 days later. Conclusion: Clinicians should be aware of GPA atypical clinical manifestations.

Case Report: Case report: An unusual presentation of granulomatosis with polyangiitis

Aim: We are reporting a case of an unusual presentation of granulomatosis with polyangiitis (GPA) with liver involvement. Case presentation: A 45-year-old male patient presented with erythematous plaques on the face and bilateral nasal obstruction. On physical examination, the patient had a ring-shaped squamous plaque on the face. The laboratory findings revealed an accelerated erythrocyte sedimentation rate at 100 mm/h, an elevated C-reactive protein at 66 mg/L, hyper gamma globulinemia 16 g/L and an elevated alkaline phosphatase (twice the upper normal limit). The craniofacial and thoracoabdominal computed tomography (CT) -scans showed ethmoid and maxillary sinusitis, low facial bone density, multiple mediastinal and hilar lymphadenopathy, diffuse small pulmonary nodules, and hepatomegaly. A cutaneous lesion biopsy, the nasal mucosa, and the liver showed a chronic inflammatory granulomatosis process with necrosis. Serum anti-neutrophil cytoplasmic antibody (ANCA) against PR3 was positive. The clinical, biological, radiological, and histological findings substantiated the diagnosis of GPA. The patient received systemic steroids combined with cyclophosphamide pulses on days 1, 14 and 28 and then he was lost to follow-up. Two-years later, he presented with a cardiac failure and skin ulcer in the right lower limb. A nasal endoscopic exam showed nasal septum cartilage perforation with resorption of the middle and inferior nasal concha. Two weeks later, he developed a diffuse alveolar hemorrhage and was therefore transferred to the intensive care unit but died of respiratory failure 3 days later. Conclusion: Clinicians should be aware of GPA atypical clinical manifestations.

Case Report: Case report: An unusual presentation of granulomatosis with polyangiitis

Aim: We are reporting a case of an unusual presentation of granulomatosis with polyangiitis (GPA) with liver involvement. Case presentation: A 45-year-old male patient presented with erythematous plaques on the face and bilateral nasal obstruction. On physical examination, the patient had a ring-shaped squamous plaque on the face. The laboratory findings revealed an accelerated erythrocyte sedimentation rate at 100 mm/h, an elevated C-reactive protein at 66 mg/L, hyper gamma globulinemia 16 g/L and an elevated alkaline phosphatase (twice the upper normal limit). The craniofacial and thoracoabdominal computed tomography (CT) -scans showed ethmoid and maxillary sinusitis, low facial bone density, multiple mediastinal and hilar lymphadenopathy, diffuse small pulmonary nodules, and hepatomegaly. A cutaneous lesion biopsy, the nasal mucosa, and the liver showed a chronic inflammatory granulomatosis process with necrosis. Serum anti-neutrophil cytoplasmic antibody (ANCA) against PR3 was positive. The clinical, biological, radiological, and histological findings substantiated the diagnosis of GPA. The patient received systemic steroids combined with cyclophosphamide pulses on days 1, 14 and 28 and then he was lost to follow-up. Two-years later, he presented with a cardiac failure and skin ulcer in the right lower limb. A nasal endoscopic exam showed nasal septum cartilage perforation with resorption of the middle and inferior nasal concha. Two weeks later, he developed a diffuse alveolar hemorrhage and was therefore transferred to the intensive care unit but died of respiratory failure 3 days later. Conclusion: Clinicians should be aware of GPA atypical clinical manifestations.

Case Report: An unusual presentation of granulomatosis with polyangiitis

Aim: We are reporting a case of an unusual presentation of granulomatosis with polyangiitis (GPA) with liver involvement. Case presentation: A 45-year-old male patient presented with erythematous plaques on the face and bilateral nasal obstruction. On physical examination, the patient had a ring-shaped squamous plaque on the face. The laboratory findings revealed an accelerated erythrocyte sedimentation rate at 100 mm/h, an elevated C-reactive protein at 66 mg/L, hyper gamma globulinemia 16 g/L and an elevated alkaline phosphatase (twice the upper normal limit). The craniofacial and thoracoabdominal computed tomography (CT) -scans showed ethmoid and maxillary sinusitis, low facial bone density, multiple mediastinal and hilar lymphadenopathy, diffuse small pulmonary nodules, and hepatomegaly. A cutaneous lesion biopsy, the nasal mucosa, and the liver showed a chronic inflammatory granulomatosis process with necrosis. Serum anti-neutrophil cytoplasmic antibody (ANCA) against PR3 was positive. The clinical, biological, radiological, and histological findings substantiated the diagnosis of GPA. The patient received systemic steroids combined with cyclophosphamide pulses on days 1, 14 and 28 and then he was lost to follow-up. Two-years later, he presented with a cardiac failure and skin ulcer in the right lower limb. A nasal endoscopic exam showed nasal septum cartilage perforation with resorption of the middle and inferior nasal concha. Two weeks later, he developed a diffuse alveolar hemorrhage and was therefore transferred to the intensive care unit but died of respiratory failure 3 days later. Conclusion: Clinicians should be aware of GPA atypical clinical manifestations.

Continuous MYD88 Activation Is Associated With Expansion and Then Transformation of IgM Differentiating Plasma Cells.

Activating mutations of MYD88 (MYD88L265P being the far most frequent) are found in most cases of Waldenström macroglobulinemia (WM) as well as in various aggressive B-cell lymphoma entities with features of plasma cell (PC) differentiation, such as activated B-cell type diffuse large B-cell lymphoma (DLBCL). To understand how MYD88 activation exerts its transformation potential, we developed a new mouse model in which the MYD88L252P protein, the murine ortholog of human MYD88L265P, is continuously expressed in CD19 positive B-cells together with the Yellow Fluorescent Protein (Myd88L252P mice). In bone marrow, IgM B and plasma cells were expanded with a CD138 expression continuum from IgMhigh CD138low to IgMlow CD138high cells and the progressive loss of the B220 marker. Serum protein electrophoresis (SPE) longitudinal analysis of 40 Myd88L252P mice (16 to 56 weeks old) demonstrated that ageing was first associated with serum polyclonal hyper gammaglobulinemia (hyper Ig) and followed by a monoclonal immunoglobulin (Ig) peak related to a progressive increase in IgM serum levels. All Myd88L252P mice exhibited spleen enlargement which was directly correlated with the SPE profile and was maximal for monoclonal Ig peaks. Myd88L252P mice exhibited very early increased IgM PC differentiation. Most likely due to an early increase in the Ki67 proliferation index, IgM lymphoplasmacytic (LP) and plasma cells continuously expanded with age being first associated with hyper Ig and then with monoclonal Ig peak. This peak was consistently associated with a spleen LP-like B-cell lymphoma. Clonal expression of both membrane and secreted µ chain isoforms was demonstrated at the mRNA level by high throughput sequencing. The Myd88L252P tumor transcriptomic signature identified both proliferation and canonical NF-κB p65/RelA activation. Comparison with MYD88L265P WM showed that Myd88L252P tumors also shared the typical lymphoplasmacytic transcriptomic signature of WM bone marrow purified tumor B-cells. Altogether these results demonstrate for the first time that continuous MYD88 activation is specifically associated with clonal transformation of differentiating IgM B-cells. Since MYD88L252P targets the IgM PC differentiation continuum, it provides an interesting preclinical model for development of new therapeutic approaches to both WM and aggressive MYD88 associated DLBCLs.

IL-2 contributes to cirrhosis-associated immune dysfunction by impairing follicular T helper cells in advanced cirrhosis

Patients with decompensated cirrhosis suffer from recurrent infections and inadequate responses to prophylactic vaccinations. However, many patients present with hypergammaglobulinemia (HGG), indicating a sustained ability to generate antibody responses. As follicular T helper (Tfh) cells are central facilitators of humoral immunity, we hypothesized that Tfh cell responses may be altered in advanced liver disease and we aimed to identify the mechanisms underlying any such alterations. Tfh, regulatory T (Treg) cells, B cells, circulating cytokines and immunoglobulins were analyzed in cohorts of patients with compensated (n= 37) and decompensated cirrhosis (n= 82) and in non-cirrhotic controls (n= 45). Intrahepatic T cells were analyzed in 8 decompensated patients. The influence of IL-2 on Tfh cell function was evaluated invitro, including Tfh cell cloning and T cell-B cell co-cultures with clones and primary tonsil-derived Tfh cells. Tfh cell frequencies were reduced in patients with decompensated cirrhosis, with phenotypic signatures indicative of increased IL-2 signaling. Soluble IL-2 receptor (sCD25) was elevated in these patients and CD4 T cells were more responsive to IL-2 signaling, as characterized by STAT5 phosphorylation. IL-2 exposure invitro diminished the Tfh phenotype and resulted in impaired Tfh helper function in co-culture experiments with naïve B cells. Tfh cells were barely detectable in cirrhotic livers. IL-2 signatures on Tfh cells in decompensated patients correlated with immunoglobulin levels, which were found to be associated with improved survival. Tfh cell impairment represents a previously underestimated feature of cirrhosis-associated immune dysfunction that is driven by IL-2. The presence of HGG in decompensated patients predicts an intact Tfh cell compartment and is associated with a favorable outcome. Patients with advanced cirrhosis often fail to generate protective immunity after prophylactic vaccinations and suffer from recurring infections that are associated with high mortality. Follicular T helper (Tfh) cells are specialized CD4 T cells that enable the emergence of antibody responses against microbial pathogens. This report demonstrates that Tfh cells are impaired in patients with advanced cirrhosis due to interleukin-2 signaling, a cytokine that is known to impair the generation of Tfh cells.

Clinicopathological analysis of six cases of disabling pansclerotic morphea

Objective To investigate clinical and pathological features of 6 cases of disabling pansclerotic morphea (DPM). Methods Clinical and pathological manifestations of and follow-up results in 6 patients, who were clinically and histopathologically diagnosed with DPM in the Department of Pathology, Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from 2007 to 2017, were retrospectively analyzed. Results Among the 6 patients, 4 were male and 2 were female. The age of onset ranged from 3 to 10 years, with an average age of 6.5 years. The average duration from the occurrence to the confirmation of the diagnosis was 6.2 years (range, 2-10 years). At all the lesional sites, skin atrophy, thining and tightness occurred, and the limbs became thin. Additionally, there were muscular atrophy and visible deep thick veins on the surface of the limbs. The contracture, deformity and dysfunction of the adjacent joints occurred in 4 cases, and the lower limbs were obviously shortened in 2 cases. Peripheral blood examination showed no increase of eosinophils or hypergammaglobulinemia. Imaging examination revealed smooth cortical bone and clear trabecular bone, and no osseous abnormality was observed. Histopathological examination of contracted skin lesions of the lower limbs revealed atrophic and thinned epidermis, hyperpigmentation in the basal layer, hyperplastic, thickened, hardened and partly homogenized collagen fibers in the middle to deep dermis, subcutaneous adipose tissue region and deep tissue of the skin. Conclusions DPM usually does not affect viscera, but often involves deep tissue of the limbs. Histopathologically, DPM is mainly characterized by obviously hyperplastic and hardened collagen fibers in the dermis and subcutaneous tissue. Key words: Scleroderma, localized; Child; Skin manifestations; Pathologic processes; Therapy; Disabling pansclerotic morphea

Clinical analysis of youth patients with retinal arterial occlusions

Objective To observe the clinical features of retinal arterial occlusion (RAO) in youth. Methods This is a retrospective case review. Nine patients (9 eyes) with RAO were enrolled in this study. There were 6 males (6 eyes) and 3 females (3 eyes). The average age was (14.22±3.93) years. The bestcorrected visual acuity (BCVA), indirect ophthalmoscopy, fundus color photography and fundus fluorescein angiography were performed. All patients underwent systemic evaluation including blood routine, erythrocyte sedimentation rate, blood lipids, vasculitis screening, homocysteine level, antiphospholipid antibody, blood coagulation, neck vascular ultrasound, and cardiac color ultrasound and electrocardiogram examination. All patients received oxygen therapy, blood medications and symptomatic treatment. Meanwhile, the patients with autoimmune diseases were received systemic glucocorticoid therapy. The follow-up was ranged from 6 to 12 months. The visual acuity and fundus change before and after treatment were compared. Results among 9 patients, one patient had systemic lupus erythematosus, one patient had congenital heart disease, one patient had hypergammaglobulinemia, and carotid artery color ultrasonography showed that the internal carotid artery vessels faltered in 2 cases. The BCVA was 0.01 - 0.12. Among 9 eyes, there were 5 eyes (55.6%) with retinal branch artery occlusion (BRAO), 2 eyes (22.2%) with central retinal artery occlusion (CRAO), 2 eyes (22.2%) with ciliary retinal artery occlusion (CLAO). CRAO eyes showed positive RAPD (relative afferent pupillary defect), fine retinal artery and the corresponding vein, pale white retinal edema in posterior area and macular cherry-red spot. BRAO eyes manifested as inferior temporal artery occlusion and pale white retinal edema around them. CLAO eyes showed temporal ligulate grey-white retinal edema. At the last follow-up, BCVA improved and retinal vessels returned to normal in 7 eyes (77.8%); BCVA unchanged and no improvement in fundus in 2 eyes (22.2%). Conclusion Adolescent RAO is mostly partial occlusion, the prognosis is generally good after early active treatment. Key words: Retinal artery occlusion/etiology; Adolescent; Prognosis

Turmeric Dietary Supplement‐Induced Autoimmune Hepatitis: A Case Report

Autoimmune hepatitis (AIH), a chronic disorder of unknown etiology characterized by hypergammaglobulinemia and autoantibody positivity, is induced by drug injury in a minority of cases. Herbal supplements are increasingly being recognized as a potential cause of drug‐induced hepatitis (DIH). We report here on a case of drug‐induced, autoimmune hepatitis (DIAIH) attributable to ingestion of a turmeric dietary supplement. Autoimmune hepatitis (AIH) was diagnosed, as per Hennes criteria (score = 7 of 8 total), in a 76‐year old Caucasian woman presenting with an asymptomatic elevation in liver transaminases (alkaline phosphatase and bilirubin, normal). Diagnostic work up was notable for: 1) elevated IgG levels (1.3 X ULN); 2) positive antibody titers (> 1:80) for atypical pANCA and smooth muscle actin; 3) liver histology on biopsy compatible with AIH, and 4) exclusion of viral hepatitis. The patient's medical records, while not including mention of turmeric dietary supplement use, did document concurrent use of 15 other prescription or over the counter (OTC) medications which remained unchanged throughout the course of transaminase elevations. Attribution of AIH to turmeric supplementation, which the patient had begun 10‐months prior to her diagnosis, was elucidated by the patient, who stopped turmeric supplementation 2 months after her AIH diagnosis upon reading of a possible risk of turmeric‐induced hepatitis. Within 1 month of turmeric discontinuation, transaminase levels, which had risen to a maximum of 4–8 X ULN (for AST and ALT, respectively) began to decline and returned to normal within a year, where they have remained until the present time (3 years). Assessment of updated RUCAM drug‐induced hepatitis (DIH) criteria (Danan et al, Int J Mol Sci 17:2016) yielded a score of 6 (of 13 total, with ≥9 being highest category of attribution [“highly probable”]), consistent with probable attribution of turmeric use to hepatic injury in this patient. As is common in situations of supplement induced side‐effects, the actual product, which the patient had taken as directed on the label, was not identified or available for testing. In summary, this case illustrates several key points: 1) consumers and healthcare professionals should be aware that turmeric supplements, a top selling herbal in the US, can be associated with hepatoxicity, including induction of AIH; 2) the role of turmeric, concomitant medications, and/or potential contaminants in mediating supplement‐induced liver damage cannot be assessed at present; and 3) open conversations about OTC supplement use between healthcare providers and patients remains imperative to ensure delivery of high quality practice, particularly in situations of increased risk of drug‐supplement interactions.Support or Funding InformationNIH‐NCCIH#R34 AT007837

Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection.

Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population. Antigen-specific antibody responses were restored by ablation of IFN-I signaling through antibody-mediated IFN-I receptor blockade and B cell-specific IFN-I receptor knockout. Importantly, IFN-I receptor deficiency in B cells also accelerated the development of LCMV neutralizing antibodies and alleviated HGG. These results provide a potential therapeutic target toward efficient treatment measures that limit immunopathology in persistent viral infections.

A case of cutaneous and systemic plasmacytosis

A 46-year-old male patient developed scatterred reddish-brown plaques and nodules on the back 6 years prior to the presentation. Then, the lesions gradually spread to the axillary fossa and protothorax, and became indurated with slight itching in winter. Laboratory examination revealed hypergammaglobulinemia. Computed tomography (CT) scan showed multiple nodular or patchy shadows in both lungs, lymphadenectasis in axillary, mediastinal and inguinal regions, and spleen enlargement. Histopathological examination of skin lesions showed granulomatous infiltrates with plenty of lymphocytes, histiocytes and mature plasma cells in the middle and lower dermis with the presence of lymphoid follicle-like structures, but no cell atypia was observed. Immunohistochemical study showed positive staining for CD38, CD138, CD79a, κ and λ light chains. According to clinical manifestations and laboratory examination results, the patient was diagnosed with cutaneous and systemic plasmacytosis. Key words: Neoplasms, plasma cell; Skin manifestations; Hypergammaglobulinemia; Plasmacytosis

Severe Toxocariasis in Children-Diagnostic Difficulties.

ABSTRACT: We present the case of an 18-month-old girl, from rural area, admitted to our clinic for fever and cough. The anamnestic data and the clinical and radiological examinations initially suggested the diagnosis of acute interstitial pneumonia. During hospitalization, she repeatedly presented exacerbations with acute respiratory failure, but without fever. Paraclinic examinations revealed anemia, leukocytosis, inflammatory tests with highly increased values, low values of serum iron and serum calcium, hyperproteinemia with hypergammaglobulinemia, the values of IgE and IgG being highly increased. Repeated pulmonary x-rays-peribronchovascular interstitial thickening, at the level of peri-and right infrahilar area. Medullary puncture-increased percentage of eosinophils in several stages of maturity, approximately 20%, normal values for the other medullary series, without atypical cells; the fingertip hemogram showed anemia, leukocytosis, eosinophilia. The diagnosis turned to a possible toxocariasis-atc anti toxocara canis=55.6 NTU. In the third week of hospitalization, the patient presented short crises of nonfebrile seizures. Normal CT and EEG brain. The child was discharged after 5 weeks, the diagnosis being severe toxocariasis with pulmonary and neurological manifestations; she was recommended an antiparasitary treatment and remained in our clinic's records.

Isolated maxillary rosai dorfmannn disease masquerading as a malignancy

Rosai Dorfmann disease (RDD), first described in 1969 by Rosai and Dorfmann, is a rare, benign disorder of unknown etiology. It is a distinct clinopathological entity, typically characterized by non Langerhan histiocytic cell proliferation with massive cervical lymphadenopathy. Axillary, mediastinal and inguinal nodes are affected rarely. Fever, anemia, leucocytosis, hypergamma globulinemia, raised ESR and rarely autoimmune hemolytic anemia may coexist; mimicking differentials like Wegener’s granulomatosis, Langerhans cell histiocytosis, Tuberculosis, Hodgkin’s lymphoma, monocytic leukaemia and rhinoscleromatosis. Hence, a high clinical suspicion with immunopathological analysis confirms the diagnosis, as in this case report.

Cutaneous and systemic plasmacytosis

Cutaneous and systemic plasmacytosis (CSP) , a rare benign disease characterized by infiltrates of mature plasma cells in various organ systems, usually affects the skin, lymph nodes and bone marrow. Clinically, it manifests as multiple reddish-brown patches, nodules and plaques symmetrically located on the face, neck, trunk and axillary fossa without any subjective symptoms. Polyclonal hypergammaglobulinemia often complicates CSP. Histopathologically, it is characterized by dense perivascular or periadnexal infiltrates of mature plasma cells in the dermis. Immunohistochemical studies usually reveal polyclonal proliferation of infiltrative plasma cells, which express both κ and λ light chains. Key words: Plasma cells; Cell proliferation; Skin diseases; Cytokines; Systemic plasmacytosis

Clinical features analysis of monoclonal immunoglobulinemia of undetermined significance transforming into multiple myeloma in the elderly

Objective To study the time of monoclonal immunoglobulinemia of undetermined significance (MIUS) transforming into multiple myeloma (MM), and the changes of immunoglobulin level and the clinical features. Methods A retrospective analysis was conducted in 22 patients with MM. According to the follow-up of immunoglobulin levels, patients were divided into formal and informal groups. The changes in immunoglobulin, serum calcium, hemoglobin and creatinine concentrations, and the time of MIUS transforming into MM were detected, and the impact of treatment on the prognosis was analyzed. Results The median age at diagnosis as MIUS was 69 years in formal group and 79 years in informal group. The median time for MIUS transforming into MM was 9.8 years in formal group and 1.3 years in informal group (P=0.006). The initial average concentration of immunoglobulin in patients with MIUS was 12.5 g/L (2.0-31.6 g/L) in informal group and 11.5 g/L (2.8-29.0 g/ L) in formal group (P>0.05). There were no significant differences in levels changes of immunoglobulin, serum calcium, hemoglobin, creatinine index before and after the outcome. The transfer time for MIUS transforming into multiple myeloma was 9.8 years and 9.7 years, and the survival time was 13.6 years and 13.5 years in patients with versus without treatment (P>0.05). Conclusions Regular formal follow-up can accurately assess the transfer time for MIUS to MM, and the transfer time is longer in formal groups than in informal group. The changes in concentrations of immune globulin, serum calcium, hemoglobin, and creatinine cannot serve as indicators for outcome evaluation. Drug treatment neither delays the progress time of MIUS to MM nor reduces the complications of MM and nor prolongs the survival time. Key words: Hypergamma-globulinemia; Multiple myeloma

Gaucherʼs disease type I: a disease masked by the presence of abnormal laboratory tests common to primary liver disease

Gaucher's disease (GD) may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy with imiglucerase. GD is associated with cytopenia, bone complications, hepatosplenomegaly, hypermetabolism, and hyperactivity of the immune system manifested by polyclonal hyper gamma-globulinemia and an increased incidence of monoclonal gammopathies. High ferritin and presence of autoimmune antibodies may present and because of these abnormalities, clinical similarities with primary liver diseases may occur. We report on two patients who suffered diagnostic delay that could potentially lead to life-threatening manifestations of GD. Potential complications include: avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, and liver pathology. Physician awareness will increase the likelihood of prompt detection of GD and improve its management.

Their titers and recognized molecules of IgG class anti-BCG antibody in sera from patients with tuberculosis

Hypergammaglobulinemia is a frequent complication of tuberculosis. Serum levels of each class of immunoglobulin were analyzed among tuberculosis patients. Adult patients had high levels of IgG and IgA, but IgM levels were not elevated. These data suggested that antibody responses to mycobacterial antigens might be influenced by individual immune responses. In order to analyze the specific antibody responses to mycobacterial antigens, IgG class antibodies reactive with BCG proteins were enumerated by an enzyme-linked immunosorbent assay (ELISA). Patients were shown to have significantly higher a mount of IgG antibodies than healthy controls. Sera from patients with active tuberculosis had high consistently titers of antibodies. Antibody titers returned to a normal range after effective treatment, suggesting that the measurement of IgG anti-BCG antibodies would be useful for the diagnosis and follow-up of tuberculosis. In addition, serum antibody profiles were analyzed by immunoblotting. Sonicated whole BCG proteins were electrophorased and transferred to nylon sheets by Western blotting. Then the sheets were developed with sera from patients or controls. Mycobacterial cell wall contains a vast array of proteins so that comparison of the antibody profiles from different sera revealed striking individual variations. However two kinds of proteins, whose molecular sizes were 65KDa and 16KDa, were considered to be significant. The 65 KDa protein was recognized in most sera from both patients and controls. The protein may be related to a "common antigen" present in a wide variety of bacteria. These observations may shed a new light on the role of 65KDa protein in the regulation of the immune systems, for example a individual highly primed to 65KDa protein may amount an exaggerated and potentially harmful response to cross-reactive antigens from other essentially non-pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

IgG4-related disease

IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions, mainly in exocrine tissue, that consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4+ plasma cells in the affected tissues, and the serum IgG4 level is elevated in these patients. Ocular adnexal IgG4-related disease frequently involves bilateral lacrimal glands, and obliterative phlebitis is rare. Moreover, some malignant lymphomas, especially mucosa-associated lymphoid tissue lymphoma, arise from ocular adnexal IgG4-related disease. It is known that hyper IL-6 syndromes, such as multicentric Castleman's disease, rheumatoid arthritis, and other autoimmune diseases, fulfill the histological diagnostic criteria for IgG4-related disease; therefore, hyper IL-6 syndromes and IgG4-related disease cannot be differentially diagnosed by immunohistochemical staining alone. However, upon laboratory examination, hype IL-6 syndromes show elevation of the CRP level, polyclonal hyper gamma-globulinemia, anemia, and hypoalbuminemia. These findings are quite different from IgG4-related disease, which is not characterized by elevated serum IgA, IgM, and CRP levels. Therefore, laboratory findings are crucial for the differential diagnosis.

Application of flow cytometry in the diagnosis of X-linked hyper-IgM syndrome

Objective To develop a flow cytometrie assay to for diagnosis of X-Linked Hyper.1gM Syndrome(XHIM).Methods Heparinized peripheral blood obtained from patient,mother and a healthy control was diluted with RPMI- 1640(unstimulated control)or with RPMI-1640 containing 15μl PMA(1 rig/μl)and 6 trl ionomycin(50 ng/μl)(stimulated cell).Using directly labeled antibodies,we have examined CD40 ligand levels on CD3+ CD8- lymphocyte surface,and CD69 levels on CD;lymphocyte Surface to determine whether the cells were activated.Results CD69 levels on CD3+ lymphocyte surface from stimulated group and from unstimulated group were above 96% and below 3%,respectively.CD40L levels Oil CD3 CDs-T lymphocyte surface from stimulated group were 0.8% (patient),60.04%(mother) and 62.87%(healthy contr01).CD40L levels on CD3+ CD8-T lymphocyte surface from unstimulated group were 0.88% (patient),4.15%(mother)and 5.51%(healthy contr01).Conclusion This flow cytometric assayis accurate and convenient,which Can be used in neonatal screening. Key words: Hypergammaglobulinemia; Immunoglobulin M; Flow cytometry