PubMed Health⌕ Search

Biomedical subjects

R U Sorensen

Publications and source records attributed to R U Sorensen.

At least 19 recordsLinked to original sources

Effects of absorption with pneumococcal type 22F polysaccharide on maternal, cord blood, and infant immunoglobulin G antipneumococcal polysaccharide antibodies.

The aim of this study was to evaluate the effect of absorption with pneumococcal type 22F polysaccharide on antipneumococcal antibody titers in unimmunized Chilean pregnant women and on antibodies in their offspring at birth and 3, 6, and 12 months of age. Sera from 10 healthy pregnant women and from their offspring at birth and at 3, 6, and 12 months of age were studied. Immunoglobulin G antibodies against serotypes 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, and 23F were measured by a standardized enzyme-linked immunosorbent assay method. All sera were absorbed with polysaccharide C, and aliquots of each serum were absorbed with polysaccharide 22F. Individual results were expressed in mug/ml based on the standard serum pool 89-SF. Absorption with polysaccharide 22F reduced antibody concentrations in all samples and to all 10 serotypes studied. Reduction was highest in maternal sera and in cord blood, but it was also present at 3, 6, and 12 months of age. The percent reduction ranged from 24% for serotype 14 to 50% for serotype 1 in maternal samples and from 20% for serotype 18C to 49% for serotype 4 in cord blood samples. The percentages of transplacental transmission were similar for nonabsorbed and absorbed maternal fetal pairs. Absorption with serotype 22F had a significant impact on antipneumococcal antibody concentrations in unimmunized pregnant women and in their offspring. Our results suggest that absorption with 22F polysaccharide needs to be performed in studies of transplacental transmission of antipneumococcal antibodies.

Absorption↗

Up-regulation of CD40 ligand and induction of a Th2 response in children immunized with pneumococcal polysaccharide vaccines.

We wished to determine whether pneumococcal polysaccharide antigens induce mRNA expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized individuals in vitro and whether immunization with the 23-valent pneumococcal polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression. Children with recurrent respiratory infections were studied before and 4 to 6 weeks after receiving the pneumococcal vaccine. One patient who failed to respond to the polysaccharide vaccine subsequently received a single dose of the experimental 7-valent pneumococcal conjugate vaccine. Unimmunized healthy adults were included as controls. Quantification of mRNA expression of CD40L, interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-gamma) was performed by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with resting and stimulated peripheral blood mononuclear cells. Serum immunoglobulin G (IgG) anti pneumococcal antibody levels were measured by ELISA. The results showed a significant increase in the expression of mRNAs for CD40L and IL-4, but not IL-12p40 or IFN-gamma, in stimulated cultures from unimmunized individuals. CD40L and IL-4 mRNA expression was significantly higher in postimmunization than in preimmunization samples stimulated with the individual pneumococcal serotypes. These results suggest that pneumococcal polysaccharide antigens specifically up-regulate CD40L expression and induce a Th2 response in vitro which parallels the increase in IgG antipneumococcal antibody levels in serum.

Adolescent↗

Influence of patient age on Streptococcus pneumoniae serotypes causing invasive disease.

All clinical S. pneumoniae specimens isolated from patients with invasive or sterile-site infections admitted to one regional general hospital in southern Chile were collected during a 5-year period (February 1994 to September 1999). A total of 247 strains belonging to 50 serotypes were isolated in this survey: 69 in patients under 5 years of age, 129 in patients 5 to 64 years old, and 49 from patients 65 years and older. Eight serotypes were identified in all age groups, while all other serotypes were found exclusively in one age group or in patients over 4 years of age. Serotype 3 was never found in patients under 5 years old, and serotype 14 was not found in patients >64 years of age. There was no difference in the serotypes causing infection in each one of the 5 years of the survey. Our results suggest that both bacterial virulence factors and host factors play an important role in the selection of S. pneumoniae serotypes causing invasive infection. Possible host factors include age-related differences in the immune response. Comparative studies with other areas of the world may help to further understanding of our observations in southern Chile.

Adolescent↗

Antibody deficiency syndromes.

Antibodies have a crucial role in protecting against infections, and antibody deficiencies are the commonest primary and secondary immunodeficiencies. Antibody deficiencies may be the only abnormality present in a patient, or they may be present and aggravate the symptoms of various other conditions. Because the presence of an antibody deficiency is difficult to predict from clinical presentation, physicians should perform an evaluation of antibody-mediated immunity, even knowing that, in many cases, the results are normal. When immunizations are included as a part of the evaluation, many patients experience a benefit from enhanced immunity against common pathogens. Some alternative practical approaches to the evaluation of patients with recurrent infections are outlined in Figure 8. Referral to a clinical immunologist can be based on the presence of recurrent infections, a positive family history without prior evaluation by a pediatrician, or abnormal immunologic findings that require an advanced evaluation. In any case, a close collaboration between pediatrician and immunologist likely will result in an accurate diagnosis and better treatment of patients with antibody-deficiency syndromes and their families.

Antibodies↗

Distribution of primary immunodeficiency diseases diagnosed in a pediatric tertiary hospital.

BACKGROUND: Advances in immunologic techniques in recent years have led to increased recognition of primary immunodeficiency disorders, with IgA deficiency the most common phenotype reported by most registries. There have also been reports of increased associated incidence of autoimmunity, allergy, and other diseases. OBJECTIVES: We wished to determine the percentage of different primary immunodeficiency disorders seen in a pediatric tertiary hospital and to determine the association of primary immunodeficiency disorders with other diseases that are not part of classic immunodeficiency disorders. METHODS: We performed a retrospective review of the patients referred to our allergy/immunology clinic for immunologic evaluation of recurrent infections during an 8-year period. We also reviewed pathology reports with postmortem diagnosis of immunodeficiencies not identified while patients were alive. RESULTS: Of the 91 patients with primary immunodeficiency disorders evaluated, the majority had predominantly antibody deficiencies (67%). The most common phenotype was specific antibody deficiency with normal immunoglobulins (23.1%), defined as inability to mount an adequate response to pneumococcal polysaccharides followed by IgG2 subclass deficiency (17.6%). These two phenotypes were diagnosed mostly in the last 2 years of the survey. Associated diseases, found in 40% of patients, were mostly allergic conditions followed by syndromic/chromosomal disorders. CONCLUSION: The study reveals that specific antibody deficiency with normal immunoglobulins followed by IgG2 subclass deficiency was the most frequently diagnosed primary immunodeficiency disorder in our patient population. It also indicates that immunodeficiency disorders should be considered in patients with other abnormalities like allergic and syndromic/chromosomal disorders that present with recurrent infections.

Child↗

CD40-CD40 ligand interaction is central to cell-mediated immunity against Toxoplasma gondii: patients with hyper IgM syndrome have a defective type 1 immune response that can be restored by soluble CD40 ligand trimer.

Cell-mediated immunity that results in IL-12/IFN-gamma production is essential to control infections by intracellular organisms. Studies in animal models revealed contrasting results in regard to the importance of CD40-CD40 ligand (CD40L) signaling for induction of a type 1 cytokine response against these pathogens. We demonstrate that CD40-CD40L interaction in humans is critical for generation of the IL-12/IFN-gamma immune response against Toxoplasma gondii. Infection of monocytes with T. gondii resulted in up-regulation of CD40. CD40-CD40L signaling was required for optimal T cell production of IFN-gamma in response to T. gondii. Moreover, patients with hyper IgM (HIGM) syndrome exhibited a defect in IFN-gamma secretion in response to the parasite and evidence compatible with impaired in vivo T cell priming after T. gondii infection. Not only was IL-12 production in response to T. gondii dependent on CD40-CD40L signaling, but also, patients with HIGM syndrome exhibited deficient in vitro secretion of this cytokine in response to the parasite. Finally, in vitro incubation with agonistic soluble CD40L trimer enhanced T. gondii-triggered production of IFN-gamma and, through induction of IL-12 secretion, corrected the defect in IFN-gamma production observed in HIGM patients. Our results are likely to explain the susceptibility of patients with HIGM syndrome to infections by opportunistic pathogens.

Adjuvants, Immunologic↗

Increase in granulocyte-macrophage-colony-stimulating factor secretion and the respiratory burst with decreased L-selectin expression in hyper-IgE syndrome patients.

BACKGROUND: The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome. OBJECTIVE: To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain these clinical observations. METHODS: The following functions were analyzed in patients with the hyper-IgE syndrome and in controls: (1) production of granulocyte-macrophage-colony-stimulating factor by peripheral blood mononuclear cells by ELISA; (2) respiratory burst and reactive oxygen intermediates production by peripheral neutrophils using the luminol-enhanced chemiluminescense technique; and (3) expression of L-selectin on granulocytes and lymphocytes by flow cytometry. RESULTS: Patients with hyper-IgE syndrome had significantly increased production of granulocyte-macrophage-colony-stimulating factor by resting or stimulated mononuclear cells, increased generation of reactive oxygen intermediates by neutrophils treated with opsonized zymosan, and reduced L-selectin expression on quiescent and activated granulocytes and lymphocytes. CONCLUSIONS: Our results suggest that an important feature of the hyper-IgE syndrome is the increased production of granulocyte-macrophage-colony-stimulating factor, which may explain the reduced L-selectin expression, decreased chemotaxis, and increased oxygen radical production and tissue damage in this disease.

Adolescent↗

Evaluating children with respiratory tract infections: the role of immunization with bacterial polysaccharide vaccine.

Antibody deficiency syndromes are an important cause of recurrent infections in children. Today it is possible to perform a complete evaluation of antibody-mediated immunity leading to a definitive diagnosis of either normal or abnormal immunity in most patients. However, the interpretation of the results of IgG subclass determinations and specific antibody responses is still being defined. At this time our recommendation is that patients who meet the criteria for an evaluation of antibody-mediated immunity be referred to subspecialists trained in this evaluation until better criteria for normal have been developed. The possibility that protective amounts of antibodies against pneumococcal serotypes may develop only transiently must be considered in patients with recurrent infections after initial improvement after immunization, especially if IgG2 subclass deficiency is also present. In the future it may be possible to use a faster and more economical approach to evaluate patients with recurrent infections by immunization with pneumococcal vaccine and then measuring IgM, IgG and IgA along with postimmunization specific antipneumococcal antibody titers 4 to 6 weeks later. For this approach to become feasible, further studies comparing the information obtained from the evaluation of pre- and postimmunization antibody concentrations with that obtained from the evaluation of postimmunization concentrations alone are needed.

Antibody Formation↗

Transplacental transmission of serotype-specific pneumococcal antibodies in a Brazilian population.

The highest incidence of severe pneumococcal infections in children occurs in the first 6 months of life; however, immunization of infants with the existing polysaccharide vaccines is ineffective. We wished to determine the prevalence of immunoglobulin G (IgG) pneumococcal antibodies in unimmunized Brazilian mothers and their transplacental transmission to term and preterm infants. Total IgG, IgG1 and -2 subclass levels, and IgG antibodies against Streptococcus pneumoniae serotypes 1, 3, 6B, 9V, and 14 were determined in 15 pairs of mothers and term newborns (gestational age, >/=37 weeks) and in 18 pairs of mothers and preterm newborns (gestational age, 32 to 36 weeks). Serotype-specific anti-pneumococcal antibodies were detected by a recently standardized enzyme-linked immunosorbent assay calibrated with the 89-SF reference serum. Varying percentages of the mothers had antibody concentrations below arbitrarily defined protective levels: 33% for serotype 1, 67% for serotype 3, 30% for serotype 6B, 52% for serotype 9V, and 22% for serotype 14. In term newborns, IgG1 concentrations were slightly higher than maternal concentrations; in preterm newborns, the concentrations were much lower. Concentrations of IgG2 in term and preterm infants were significantly lower than in the mothers. Transplacental transmission of antibodies to serotypes 3 and 14 was clearly different from that of antibodies to serotypes 1, 6B, and 9V. Concentrations of IgG antibodies against serotypes 3 and 14 were similar to or higher than those of the mothers; against serotypes 1, 6B, and 9V they ranged from 77 to 83% of maternal concentrations in term newborns and also in preterm infants, although transplacental transmission of antibodies was proportionally lower for each specific serotype in preterm than in term infants. These data are relevant for developing strategies to protect infants against pneumococcal infections in the first months of life. Our findings and a review of existing information stress the importance of understanding the relationships among pneumococcal immunization, IgG subclass antibodies to individual serotypes, transplacental transport, half-life, and antibody function and their protective values against infection.

Adolescent↗

Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immunoglobulin concentrations.

BACKGROUND: A deficient antibody response to polysaccharide antigens is determined by measuring the response to the 23-valent pneumococcal polysaccharide vaccine. However, the diagnosis of this specific antibody deficiency is hampered by the lack of sufficient data and standardized testing of the response to pneumococcal polysaccharides. METHODS: All patients evaluated in our allergy/immunology clinic for recurrent respiratory infections between 1995 and 1997 without immunoglobulin, IgG subclass, or other known primary or secondary immunodeficiency were included in this analysis. IgG antipneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F, and 23F were determined by a modified ELISA protocol. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer of 1.3 microg/ml or greater or at least four times the baseline value. RESULTS: A total of 113 patients fulfilling the criteria for inclusion in this analysis were divided into five age groups. The geometric means for preimmunization and postimmunization pneumococcal antibody titers for all serotypes increased with age. For post-immunization antibody concentrations, there was a sharp increase in the specific antibody concentrations in adults in comparison with all pediatric age groups ranging in age from 7 months to 16 years. Similarly, the number of serotypes to which there was an adequate response also increased with age. CONCLUSION: We conclude that the definition of what constitutes an adequate response to pneumococcal immunization needs further definition. It is clear, however, that age has an important influence on the intensity of the response to most pneumococcal polysaccharides. Correlation studies between antibody concentrations in different IgG subclasses, functional studies, and protection studies against mucosal and invasive pneumococcal infections are in progress, and these should contribute to a refined definition of a normal response. The availability of a standardized method for the measurement of IgG antibodies against relevant pneumococcal serotypes is an important step toward this goal.

Adolescent↗

Interleukin 4 and interferon-gamma secretion by antigen and mitogen-stimulated mononuclear cells in the hyper-IgE syndrome: no TH-2 cytokine pattern.

BACKGROUND: Enhanced production of TH-2 cytokines plays a key role in increased IgE production in allergic diseases. Reports about the cytokine profile secreted by peripheral blood mononuclear cells of patients with hyper-IgE syndrome, however, are controversial, suggesting alternative causes for increased IgE production in this syndrome. OBJECTIVE: We wished to determine whether mononuclear cells from patients with hyper-IgE syndrome have a pattern of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production characteristic of a predominance of TH-2 cells and whether the cytokine production pattern is constant over time. METHODS: IL-4 and IFN-gamma secretion by peripheral blood mononuclear cells stimulated with phytohemagglutinin and D. pteronyssinus was measured by ELISA in culture supernatants. Patients with the hyper-IgE syndrome were evaluated 3 times at 4-week intervals and compared with asthmatic patients and normal subjects. RESULTS: In PHA-stimulated cultures, patients with hyper-IgE syndrome had an IL-4 and IFN-gamma secretion similar to that of controls, while asthmatic patients had increased IL-4 and decreased IFN-gamma production. Cultures stimulated with D. pteronyssinus showed a variable pattern of secretion for both cytokines. CONCLUSIONS: In allergic diseases, increased serum IgE level is the result of a TH-2 pattern of cytokine production, with high IL-4 and decreased IFN-gamma protein secretion. The increased serum IgE concentration typical of the hyper-IgE syndrome is likely the result of a different immunoregulatory process.

Adolescent↗

Topical sodium cromoglycate in the treatment of moderate-to-severe atopic dermatitis.

BACKGROUND: Unsatisfactory treatment results for severe atopic dermatitis have led to many experimental therapies, including cromolyn sodium in various vehicles at concentrations ranging from 1% to 10%. Results suggest that the vehicle used to deliver the cromolyn is relevant to its effectiveness. OBJECTIVE: To test the efficacy of low concentrations of cromolyn in a water-soluble vehicle in the treatment of moderate-to-severe atopic dermatitis in a double-blind, placebo-controlled study. METHODS: Twenty-six pediatric patients who had failed to respond to conventional therapy were randomized into 2 treatment groups: patients in group A used the study drug for 1 month (phase I), then received the placebo for 1 month (phase II); and patients in group B used the placebo for 1 month, then received the study drug for 1 month. The study drug was cromolyn sodium inhalation solution mixed into a water-based emollient cream to a final concentration of 0.21%. Upon enrollment and at each follow-up visit, every patient was given a severity score based on extent and severity of skin involvement. RESULTS: At enrollment, there were no significant differences between groups A and B in severity scores, age, sex, race, skin test and/or RAST positivity, eosinophil levels, IgE concentrations, or the presence of concomitant rhinitis or asthma. After the first phase of the study treatment, severity scores had decreased significantly for both groups with a significant difference between group A (cromolyn) and group B (placebo). After crossover, both groups had significantly lower severity scores than at entry into the study. CONCLUSION: Treatment with topical cromolyn in a hydrophilic emollient vehicle has a significant anti-inflammatory effect on moderate-to-severe atopic dermatitis. We have now incorporated this treatment into our clinical practice.

Administration, Topical↗

Primary immunodeficiency diseases in Latin America: first report from eight countries participating in the LAGID. Latin American Group for Primary Immunodeficiency Diseases.

The Latin American Group for Primary Immunodeficiencies, formed in 1993, presently includes 12 countries. One goal was to study the frequency of primary immunodeficiencies in various regions of the American continent and to enhance knowledge about these diseases among primary-care physicians, as well as allergist-immunologists. Important for this purpose was the development of a registry of primary immunodeficiencies using a uniform questionnaire and computerized database. To date, eight countries have collected information on a total of 1428 patients. Predominantly antibody deficiencies were reported in 58% of patients, followed by cellular and antibody immunodeficiencies associated with other abnormalities in 18%, immunodeficiency syndromes associated with granulocyte dysfunction in 8%, phagocytic disorders in 9%, combined cellular and antibody immunodeficiencies in 5%, and complement deficiencies in 2% of patients. The information gathered from this initial analysis of data will serve to expand the patient database to more areas within participating countries and to new countries and to increase collaboration toward better diagnosis and treatment of these diseases.

Humans↗

Central nervous system toxoplasmosis with an increased proportion of circulating gamma delta T cells in a patient with hyper-IgM syndrome.

Hyper-IgM syndrome represents a diverse group of immunodeficiencies characterized by normal or high serum IgM concentrations with decreased or absent IgG, IgA, and IgE. The X-linked form of hyper-IgM syndrome is caused by mutations in the CD40 ligand gene, preventing its expression on activated T cells. The CD40 ligand--CD40 interaction is critical for effective isotype switching and for initiating antigen-specific Tf cell responses. In addition to recurrent pyogenic infections, patients with the CD40L defect also have opportunistic infections. An increased proportion of circulating gamma-delta T cells, shown to be important early during primary infections, has been demonstrated in numerous infectious diseases including toxoplasmosis. Here, we report a patient with hyper-IgM syndrome and CNS toxoplasmosis, who showed a marked increase in gamma-delta T cells in his peripheral blood and who has responded well to treatment of his toxoplasmosis and to high-dose immunoglobulin replacement therapy.

Aging↗

Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine.

OBJECTIVE: To determine whether children with recurrent respiratory infections who failed to respond to the conventional polysaccharide vaccine would respond to a pneumococcal conjugate vaccine. METHODS: Children referred to our clinic for recurrent respiratory infections who had no known primary or secondary immunodeficiencies were immunized with a 23-valent pneumococcal polysaccharide vaccine. IgG antibodies to pneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme-linked immunosorbent assay before and 4 to 6 weeks after immunization. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer > or =1.3 microg/ml or at least 4 times the preimmunization value. Immunization with an experimental CRM197-heptavalent pneumococcal conjugate vaccine was offered to patients without an adequate response to 4 or more vaccine serotypes (nonresponders). Post-conjugate immunization antibody concentrations were measured 4 to 6 weeks later. RESULTS: In nonresponder patients (n = 17) geometric mean post-conjugate immunization (C) serum antibody concentrations (microg/ml) compared with post-polysaccharide (PS) concentrations were: (serotype, C vs. PS) 4, 1.11 vs. 0.30 (P = 0.000227); 6B, 0.46 vs. 0.20 (P = 0.017267); 9V, 0.82 vs. 0.29 (P = 0.002163); 14, 1.88 vs. 0.27 (P = 0.000615); 18C, 0.98 vs. 0.32 (P = 0.021962); 19F, 1.24 vs. 0.34 (P = 0.002844); and 23F, 0.87 vs. 0.16 (P = 0.000194). In responder patients (n = 67), after 1 dose of the polysaccharide vaccine, geometric mean antibody concentrations were: 4, 1.05; 6B, 0.96; 9V, 1.55; 14, 1.65; 18C, 1.62; 19F, 1.30; and 23F, 1.02. CONCLUSIONS: Our results show that a pneumococcal conjugate vaccine is capable of inducing an IgG response in patients with recurrent infections who had failed to mount an adequate response to the polysaccharide vaccine. Conjugate vaccines may be of value in the management of children with recurrent pneumococcal respiratory infections.

Adolescent↗

Capsular serotype and antibiotic resistance of Streptococcus pneumoniae isolates in two Chilean cities.

We compared the incidence of nasopharyngeal colonization by Streptococcus pneumoniae, the serotypes causing mucosal and invasive diseases, and the antibiotic resistance of these strains in patients admitted to three large hospitals and children attending day care centers in two Chilean cities (Santiago and Temuco). The populations in both cities were similar in ethnic background, socioeconomic status, family size, and access to medical care. Significant differences in nasopharyngeal colonization rates, in serotypes causing infections, and in antibiotic resistance were found between the two cities. In children 0 to 2 years of age, 42% were colonized with S. pneumoniae in Santiago compared to 14% in Temuco. A total of 41 serotypes were identified in both Chilean cities studied. Six serotypes were found only in Santiago; 14 serotypes were found only in Temuco. Antibiotic-resistant serotypes 6A, 6B, 14, 19F, and 23F were detected only in Santiago. We show that important differences in the incidence of nasopharyngeal carriage, infection, and S. pneumoniae serotypes can exist in similar populations in different areas of the same country. Our findings are relevant for prevention strategies, antibiotic usage, and vaccine design.

Adolescent↗

Increased circulating levels of soluble HLA class I heterodimers in patients with sickle cell disease.

This study examined the presence of a persistent state of low-grade inflammation in sickle cell anemia patients by measuring circulating sHLA-I heterodimers and C-reactive protein during the steady state and after recent crises. Thirty-nine pediatric sickle hemoglobinopathy patients were studied during the steady state and 11 patients were evaluated within 1 month of a painful crisis. A disease severity score was generated for each patient, and soluble HLA-I (sHLA-I) and C-reactive protein levels were determined. Soluble HLA-I was significantly elevated in 55% of the steady-state group and in 36% of the recent-crisis group. The percentage of patients with elevated sHLA-I differed in the various disease subgroups in the steady state: 46% of Hb SS patients, 70% of Hb SC patients, 75% of Hb S beta-thal patients, and 20% of Hb SSF patients. Steady-state and recent-crisis sHLA-I levels were not significantly different. C-reactive protein levels were elevated in 11% of steady-state patients and in 9% of recent-crisis patients. Soluble HLA-I levels did not correlate with C-reactive protein levels or disease severity score, age, hemoglobin, reticulocyte count, platelet count, or white cell count. These results show that the majority of sickle hemoglobinopathy patients have elevated sHLA-I levels during the steady state and after recent crisis, suggesting the presence of chronic inflammation during the steady state.

Anemia, Sickle Cell↗