Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus

Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.     

Humoral and cellular immune response after measles vaccination in Taiwan.

Measles immunoglobulin G (IgG) seroepidemiologic studies have been widely used to monitor the effectiveness of measles immunization programs in Taiwan. However, studies about cellular immunity against the measles virus have been lacking. This study surveyed cellular immunity after measles, mumps and rubella combined vaccine (MMR) immunization in Taiwan. Seventy six people between 1 and 80 years of age were enrolled. All patients lived in northern Taiwan, and none of them had immunodeficient disease. Every enrolled patient donated a tube of heparinized blood between January 2004 and June 2004 for cross-sectional studies of IgG seroepidemiologic and MMR-specific lymphoproliferative response. The results showed that the current 3-dose (measles x 1 + MMR x 2) measles immunization program induced slightly higher IgG seroprevalence (100% vs 85%, p=0.244) and a higher frequency of significant (stimulation indices > or = 3) MMR-specific lymphoproliferative response (50% vs 15%, p=0.044) than a 2-dose (measles x 1 + MMR x 1) immunization program, although there was no difference in IgG titers and stimulation indices. Furthermore, the population aged older than 36 years (pre-immunization era) had higher IgG titers and seroprevalence, and similar MMR-specific lymphoproliferative responses to that of the population aged younger than 36 years (post-immunization era). In summary, with the limited data, the current 3-dose (measles x 1 + MMR x 2) measles immunization policy probably more effectively induces humoral and cellular immunity than the 2-dose (measles x 1 + MMR x 1) policy. Measles IgG seroprevalence in populations of different age groups exceeds nearly 90%. Measles has been eliminated temporarily in Taiwan. For a better understanding of the durability of vaccine-induced immunity and in order to establish the most appropriate immunization schedule, long-term and large-scale prospective studies of measles-specific seroepidemiology and cellular immunity will be needed.     

Humoral and cellular immune responses in Aspergillus fumigatus pulmonary disease.

This study was designed to evaluate immunologic differences between aspergilloma (A) and allergic bronchopulmonary aspergillosis (ABPA), comparing the results to atopic and nonatopic control subjects. Humoral studies included skin tests with common inhalant antigens and Aspergillus fumigatus. Total and specific IgE and other immunologlobulin levels and serum precipitins were evaluated against A. fumigatus. Cellular immunity was studied with routine skin testing and phytohemaqglutinin-induced lymphocyte blast transformation. Antigen-induced blast transformation was also carried out with the use of serial dilutions of A. fumigatus. All patients with ABPA were atopic and had marked elevations of IgE. None of the patients were atopic and they had normal IgE levels. Immediate and late skin reactivity to A. fumigatus was low in control and A groups but high in 2 patients with ABPA. IgG antibody against A. fumigatus was generally greater in the ABPA group. Both ABPA and A had serum precipitating antibody against A. fumigatus. The atopic controls had elevated IgE levels and immediate skin test reactivity to A. fumigatus, and one also had weak serum precipitins against A. fumigatus. IgE antibody against A. fumigatus was generally higher in ABPA than A. ABPA and A patients had elevated stimulation indices (SI) to A. fumigatus. No stimulation could be detected with cells from control subjects. This study indicates that both T and B cell sensitization may play a role in the development of or as a response to aspergillus-related pulmonary disease.     

Humoral and cellular immune parameters in untreated and phenytoin- or carbamazepine-treated epileptic patients

The peripheral blood lymphocyte subsets, serum immunoglobulins (Ig A, G, M), and C3 and C4 complement protein concentrations were determined in 40 healthy subjects, 30 phenytoin-treated, 22 carbamazepine-treated and 38 untreated epileptic patients. The levels of B-lymphocytes, IgM and C3 complement proteins were found to be significantly higher in untreated epileptics than in healthy controls (P<0.01, P<0.02 and P<0.05, respectively). The absolute number of B-lymphocytes appeared to be unaffected by phenytoin or carbamazepine treatment; however, IgM levels were significantly lower in carbamazepine-treated patients than both epileptic (P<0.01) and healthy (P<0.05) controls. Phenytoin-treated patients had a significant reduction in the mean IgA and IgG levels compared to healthy and epileptic controls (P<0.05). With both drug treatments, significantly lower T-suppressor lymphocyte counts and thus higher T-helper to T-suppressor lymphocyte ratios were observed with respect to healthy and epileptic controls. Our results demonstrate that while phenytoin decreases serum IgA and IgG levels, carbamazepine reduces IgM levels significantly, and untreated epileptics show immune profiles significantly different to those of healthy subjects, suggesting that epilepsy per se may be associated with certain immune aberrations induced by antiepileptic drugs.     

Humoral immune response in patients with hemophilia

Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses.     

Humoral immune response in patients with IgA and IgM glomerulonephritis.

A single dose of inactivated mumps virus vaccine was administered to male patients with IgA glomerulonephritis (IgA-GN), IgM glomerulonephritis (IgM-GN) and to healthy males. Antibodies to mumps virus were determined using an enzyme-linked immunosorbent assay. Patients with IgA-GN showed a higher and more sustained IgG and IgA antibody response compared to patients with IgM-GN or healthy controls. Before vaccination, patients with IgM-GN had higher levels of IgG antibodies than the controls or those with IgA-GN. However, the IgA antibody and IgG responses after vaccination were low. IgM antibody responses did not vary among the groups studied. It is concluded that patients with IgA-GN are high responders for IgA and IgG antibody production. Patients with IgM-GN are low responders, especially for IgA antibody.     

Humoral and cellular immune response of the rat to immunization with bee venom.

Lewis rats were immunized with bee venom allergen in Freund's complete adjuvant (FCA) or with FCA only. Animals immunized with bee venom developed specific IgG antibodies but no specific IgE antibodies were detected. Lymphocytes from lymph nodes when cultured with antigen in vitro showed an increased stimulation index from day 17 onwards. A concomitant augmentation of T suppressor cells was observed; the T helper/T suppressor cell ratio declined from 4.5:1 before immunization to 1:1 from day 5 onwards.     

Humoral and cellular immune responses to Trypanosoma cruzi-derived paraflagellar rod proteins in patients with Chagas' disease

Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4(+) CD25(+) and CD4(+) CD69(+) lymphocytes, as well as that of small CD8(+) CD25(+) lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-gamma) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-gamma upon stimulation with PFR. PFR enhanced the percentages of IFN-gamma-producing cells in both CD3(+) and CD3(-) populations. Within the T-cell population, large CD4(+) T lymphocytes were the main source of IFN-gamma.     

Fc receptors on granulocytes from patients with rheumatoid arthritis and Felty's syndrome.

Receptors for the Fc part of IgG on polymorphonuclear cells (FcR) of patients with rheumatoid arthritis (RA), Felty's syndrome (FS) and healthy controls (HC) were studied by means of a rosetting technique with rabbit IgG coated ox erythrocytes. When cold isolated polymorphonuclear cells (PMN) were incubated at room temperature the percentage of rosette forming PMN (RF-PMN) from HC was more than twice that measured directly after isolation at 4 degrees C. The same phenomenon was observed for PMN from patients with RA although the RF-PMN increased by only 1/3. In contrast warming of PMN from patients with FS did not influence the RF-PMN. The presence of surface bound immunoglobulins and intracytoplasmic immunoglobulins was measured by immunofluorescence and appeared to be inversely related to the RF-PMN. A good correlation between the results of the C1q binding assay (C1qBA) and the immunofluorescence score was observed but no correlation existed between the C1qBA and the RF-PMN. These results indicate that the number of PMN expressing FcR in patients with RA and FS is decreased presumably because of the phagocytosis of immune complex like material. The decrease in the availability of FcR may influence the functions of the PMN.     

Humoral and cellular immunity against allogeneic antigens in patients with acute leukaemia.

The humoral and cellular immunity of 12 patients with acute leukaemia (6 AML and 6 ALL) was investigated using several techniques. The study of the humoral response included the screening for allogeneic and autologous lymphocytotoxins, for cytotoxic antibodies against leukaemic blasts, Daudi cells and B lymphocytes and the detection of immune complexes. The cellular immunity was investigated by stimulation of remission lymphocytes by autologous blast cells or allogeneic lymphocytes in mixed cell cultures. Most patients have retained their humoral and cellular immune responsiveness against allogeneic antigens while there seems to be no significant response against leukaemia-associated antigens.     

Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant.

Helicobacter pylori is a major cause of chronic antral gastritis and peptic ulcer disease. Further definition is needed of the factors that determine whether infected individuals remain asymptomatic, or ultimately develop ulceration of the mucosa or transformation to malignancy. To explore the possibility that host response to H. pylori may play a role in the outcome of this infection, we have examined humoral and cellular recognition of several H. pylori proteins by seropositive and seronegative persons. A complex mixture of water-extractable cell proteins, which did not include lipopolysaccharide (LPS), was recognized by serum antibodies only in seropositive or infected individuals. IgG from seropositive subjects also bound to urease and to a heat shock protein (hsp)60 that is homologous to the 65-kD mycobacterial heat shock protein, while sera from uninfected individuals were negative. Although antibody responses to these antigens were restricted to seropositive subjects, T cell recognition of the same proteins was found in both seropositive and seronegative subjects. The water extract of H. pylori stimulated peripheral blood mononuclear cells (PBMC) from all subjects, while purified proteins activated lymphocytes of only some seropositive and seronegative subjects. PBMC that were activated by the H. pylori hsp60 did not respond to the autologous human p60 heat shock protein. These results demonstrate that, in contrast to antibody responses, T cell recognition of H. pylori proteins may occur in non-infected persons. In addition, the data suggest that in these subjects, peripheral lymphocytes that are activated by bacterial heat shock proteins do not mediate tissue damage by recognition of human heat shock homologues.     

献血者乙型肝炎病毒体液免疫和细胞免疫水平研究

目的:研究自然状态下献血者对乙型病毒性肝炎不同抗原成份的体液、细胞免疫应答水平,及两者的相关性。方法:ELISA检测献血者血浆中HBsAb、HBcAb、preS1+S2-Ab的阳性率,ELISOPT检测外周血单个核细胞中抗原特异性IFN-γ分泌细胞水平。结果:体液免疫应答检测结果表明preS1+S2-Ab的检出率最高,占85.7%(48/56),核心杭体的检出率最低30.4%(17/56);特异性细胞免疫检测结果提示献血者总体preS1+S2-Ag、HBcAg的特异性细胞免疫应答水平有着良好的一致性,无统计学差异(P>0.05),但显著优于HBsAg;preS1+S2-Ag和HBsAg特异性细胞免疫和体液免疫应答有着较好的一致性,但HBcAg特异性细胞免疫和体液免疫无明确关联(P>0.05)。结论:自然状态下献血者对乙型病毒性肝炎不同抗原成份均有较好的体液、细胞免疫应答,preS1+S2的体液免疫应答水平优于表面及核心抗原提示人HBV疫苗的侯选对象。     

Humoral and cellular immunity to papillomavirus in patients with cervical dysplasia

The cell-mediated and humoral immune responses to human papillomavirus (HPV) were tested in groups of patients with various degrees of cervical intraepithelial neoplasia (CIN) using a lymphocyte proliferation assay (LPA) as a measure of circulating sensitised T-cells and an enzyme-linked immunosorbent assay (ELISA) for antibodies. Twenty-three of 92 patients (25%) gave stimulation indices (S.I.) greater than two to at least one of the several antigen preparations tested in the LPA. Of 282 patients, 144 (50.1%) showed ELISA indices (E.I.) greater than one to HPV-1 and/or HPV-2 antigens prepared by disruption of purified virions. No correlation was found between positive responses in either test and the presence in cervical biopsies of koilocytes (considered pathognomonic for HPV infections), or between positive responses and the degree of dysplasia observed. Rather, positive antibody and T-cell responses corresponded with a history of past or present skin warts. Although antibody was detected in 42/86 (48.8%) women who thought they had never had warts, only 2/24 (8.3%) with no known history gave a positive S.I. in LPA.     

Humoral and cellular immune responses to experimental Fasciola hepatica infections in goats

Humoral and cellular immune responses to Fasciola hepatica excretory-secretory products (ESPs) in primary and secondary experimental infections in goats were studied. Primary infection induced the development of chronic subclinical fascioliasis that did not affect the establishment of flukes coming from the secondary infection, as the same percentages of recovered flukes were found in both groups. The specific IgG response to F. hepatica ESPs was similar in primary and secondary infections; challenge flukes did not induce any modification in the IgG response. The specific lymphocyte response to F. hepatica ESPs was absent in most of the infected goats, both primarily and secondarily infected. A modulation of the nonspecific cellular responses to mitogens was also observed. All infected goats showed a reduced proliferative response to concanavalin A and phytohemagglutinin. According to our results, humoral and cellular responses to F. hepatica ESPs in goats have no protective effect on the establishment of flukes and the development of disease in either primary or secondary infections. Received: 13 February 1997 / Accepted: 24 March 1997     

Humoral and cellular immune response to thyroglobulin in different inbred rat strains

The role of humoral and cellular immunity in experimental autoimmune thyroiditis was examined in inbred rat strains. A significant relationship between thyroiditis and both in vitro proliferative responses to rat thyroglobulin and in vivo delayed hypersensitivity (ear test) was observed in responsive rats. Comparison of the autoantibody response and thyroiditis among rat strains revealed no direct correlation of RT1 genotype with either parameter.     

GM-CSF and G-CSF in Felty's syndrome

Summary The risk of infection is increased in patients with Felty's syndrome, neutropenia being one of the main reasons for the susceptibility to infection. We report the case of a 56-year-old patient with Felty's syndrome in whom successive therapy with GM-CSF, splenectomy, and G-CSF was tried because of recurrent severe infections. Therapy with GM-CSF and G-CSF resulted in improvement of neutropenia and in successful treatment of cutaneous and pulmonary infections.Abbreviations GM-CSF granulocyte-macrophage colonystimulating factor - G-CSF granulocyte colony-stimulating factor Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Humoral and cellular immune reactions 'in vitro' against allogeneic and autologous human melanoma cells.

Based on 51Cr release from an allogeneic human melanoma cell (M1) cell-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were determined in twenty-eight melanoma patients, thirty-one healthy controls, ten patients with other tumours and eleven chronic lymphocytic leukaemia (CLL) patients. The results were related to simultaneously performed microcytotoxicity (MC) tests, HL-A typing, plasma membrane fluorescence and B:T cell ratios in the peripheral blood. Furthermore, lymphocytes from six melanoma patients were tested in CMC and ADCC assays against autologous tumour cells. The following results were obtained. (1) A large number of healthy controls possessed lymphocytes which readily lysed M1 target cells in CMC and MC assays. (2) CMC activity of lymphocytes from melanoma patients was generally lower than that of control lymphocytes and decreased further with progression of the disease. (3) CLL lymphocytes were virtually non-toxic for M1 cells, even at high aggressor:target cell ratios. (4) ADCC assays with a heterologous rabbit-anti-M1 serum showed generally higher isotope release than CMC assays; this was particularly pronounced in the melanoma group and in the group of patients with other tumours. (5) No tumour-specific blocking factor could be detected in melanoma sera, as judged by the capacity of the sera to block CMC activity. (6) No obvious correlation was found between the results obtained in short-term CMC and long-term MC assays. (7) T lymphocytes, as determined by E-rosette formation, were significantly diminished in melanoma patients. (8) The HL-A type of lymphocytes from normal donors and melanoma patients did not appear to be related to high or low activity in CMC and MC assays. (9) Preliminary results of 51Cr release tests with autologous melanoma cells were encouraging with respect to the correlation of the results to the clinical course of the disease.     

Humoral immune mechanisms involved in protective and pathological immunity during COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is associated with excessive inflammation, as a main reason for severe condition and death. Increased inflammatory cytokines and humoral response to SARS-CoV-2 correlate with COVID-19 immunity and pathogenesis. Importantly, the levels of pro-inflammatory cytokines that increase profoundly in systemic circulation appear as part of the clinical pictures of two overlapping conditions, sepsis and the hemophagocytic syndromes. Both conditions can develop lethal inflammatory responses that lead to tissue damage, however, in many patients hemophagocytic lymphohistiocytosis (HLH) can be differentiated from sepsis. This is a key issue because the life-saving aggressive immunosuppressive treatment, required in the HLH therapy, is absent in sepsis guidelines. This paper aims to describe the pathophysiology and clinical relevance of these distinct entities in the course of COVID-19 that resemble sepsis and further highlights two effector arms of the humoral immune response (inflammatory cytokine and immunoglobulin production) during COVID-19 infection.