Rituximab and improved nodular regenerative hyperplasia-associated non-cirrhotic liver disease in common variable immunodeficiency: a case report and literature study.

Common variable immunodeficiency (CVID) associated liver disease is an underrecognized and poorly studied non-infectious complication that lacks an established treatment. We describe a CVID patient with severe multiorgan complications, including non-cirrhotic portal hypertension secondary to nodular regenerative hyperplasia leading to diuretic-refractory ascites. Remarkably, treatment with rituximab, administered for concomitant immune thrombocytopenia, resulted in the complete and sustained resolution of portal hypertension and ascites. Our case, complemented with a literature review, suggests a beneficial effect of rituximab that warrants further research.

Evaluating Drug Prescription Patterns in Undiagnosed Common Variable Immunodeficiency Patients.

OBJECTIVE: To compare the consumption of antibiotics (AB), systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding the diagnosis of common variable immunodeficiency (CVID) among CVID patients and matched controls and to estimate whether the level of consumption was associated with the risk of a subsequent CVID diagnosis. METHODS: We conducted a nested case-control study, identifying all individuals (n=130 cases) diagnosed with CVID in Denmark (1994-2014) and 45 age- and sex-matched population controls per case (n=5850 controls) from national registers. Drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals. RESULTS: In the 3 years preceding a CVID diagnosis, we observed more frequent and higher consumption of all three drug classes. The association between consumption and risk of subsequent CVID diagnosis was statistically significant for all drug classes. The association was stronger with higher consumption and shorter time to CVID diagnosis. The fraction of cases compared to the controls redeeming ≥1 prescription of the included drugs during the study period was higher for AB (97% vs 52%), systemic steroids (35% vs 7.4%), and inhaled bronchodilators/glucocorticoids (46% vs 11.7%) (p<0.001). CONCLUSION: CVID patients have significantly higher use of AB, systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding CVID diagnosis than controls. Prescribing these drugs in primary healthcare could be an opportunity to consider (proactive) screening for CVID. Further studies are needed to identify optimal prescription cutoffs that could endorse its inclusion in public health policies.

Recurrent Campylobacter jejuni Enteritis in a Patient with Common Variable Immunodeficiency Over an Eight Year Period.

BACKGROUND: In this case, we report multiple isolations of C. jejuni in a patient with common variable immunodeficiency between 2010 and 2018. METHODS: C. jejuni was investigated in the stool samples of the patient by classical culture method using selective media under microaerophilic atmosphere. Antibiotic susceptibilities of the strains were determined by disk diffusion method. RESULTS: Eight C. jejuni strains were isolated from the patient. All strains were resistant to ciprofloxacin. An erythromycin susceptible isolate was replaced by a resistant strain within a one- and four-month period. An erythromycin resistant isolate was replaced by a susceptible one within a year. The patient recovered all episodes by intravenous immunoglobulin replacement and antibiotherapy. CONCLUSIONS: Prolonged or recurrent C. jejuni infections should not be overlooked in immunosuppressed patients. The fact that antibiotic susceptibility may change should also be kept in mind.

Rituximab Monotherapy Is Effective as First-Line Treatment for Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in CVID Patients.

Granulomatous lymphocytic interstitial lung disease (GLILD) represents a fatal immune dysregulatory complication in common variable immunodeficiency (CVID). Evidence-based diagnostic guidelines are lacking, and GLILD treatment consists in immunosuppressive drugs; nonetheless, therapeutical strategies are heterogeneous and essentially based on experts' opinions and data from small case series or case reports.We aimed to evaluate the efficacy and safety of first-line Rituximab monotherapy for CVID-related GLILD, by assessing symptoms and quality of life alterations, immunological parameters, pulmonary function tests, and lung computed tomography.All six GLILD patients received Rituximab infusions as a first-line treatment. Rituximab was administered at 375 mg/m2 monthly for six infusions followed by maintenance every 3 months; none of the patients experienced severe adverse events. Symptom burden and quality of life significantly improved in treated patients compared to a control group of CVID patients without GLILD. Rituximab treatment indirectly caused a trend toward reduced T-cell activation and exhaustion markers sCD25 and sTIM-3. Lung function improved in treated patients, with statistically significant increases in TLC and DLCO. Lung CT scan findings expressed by means of Baumann scoring system displayed a reduction in the entire cohort.In conclusion, first-line monotherapy with Rituximab displayed high efficacy in disease remission in all treated patients, with improvement of symptoms and amelioration of quality of life, as well as restoration of PFTs and lung CT scan findings.

Common and Uncommon CT Findings in CVID-Related GL-ILD: Correlations with Clinical Parameters, Therapeutic Decisions and Potential Implications in the Differential Diagnosis.

PURPOSE: To investigate computed tomography (CT) findings of Granulomatous Lymphocytic Interstitial Lung Disease (GL-ILD) in Common Variable Immunodeficiency (CVID), also in comparison with non-GL-ILD abnormalities, correlating GL-ILD features with functional/immunological parameters and looking for GL-ILD therapy predictive elements. METHODS: CT features of 38 GL-ILD and 38 matched non-GL-ILD subjects were retrospectively described. Correlations of GL-ILD features with functional/immunological features were assessed. A logistic regression was performed to find a predictive model of GL-ILD therapeutic decisions. RESULTS: Most common GL-ILD CT findings were bronchiectasis, non-perilymphatic nodules, consolidations, Ground Glass Opacities (GGO), bands and enlarged lymphnodes. GL-ILD was usually predominant in lower fields. Multiple small nodules (≤10 mm), consolidations, reticulations and fibrotic ILD are more indicative of GL-ILD. Bronchiectasis, GGO, Reticulations and fibrotic ILD correlated with decreased lung performance. Bronchiectasis, GGO and fibrotic ILD were associated with low IgA levels, whereas high CD4+ T cells percentage was related to GGO. Twenty out of 38 patients underwent GL-ILD therapy. A model combining Marginal Zone (MZ) B cells percentage, IgA levels, lower field consolidations and lymphnodes enlargement showed a good discriminatory capacity with regards to GL-ILD treatment. CONCLUSIONS: GL-ILD is a lower field predominant disease, commonly characterized by bronchiectasis, non-perilymphatic small nodules, consolidations, GGO and bands. Multiple small nodules, consolidations, reticulations and fibrotic ILD may suggest the presence of GL-ILD in CVID. MZ B cells percentage, IgA levels at diagnosis, lower field consolidations and mediastinal lymphnodes enlargement may predict the need of a specific GL-ILD therapy.

Clinical Features, Immunological Characteristics, and Treatment Outcomes of Campylobacter spp. Infections in Patients With Common Variable Immunodeficiency.

BACKGROUND: Campylobacter infection usually causes a self-limited clinical illness lasting 5 to 7 days, resolving without antimicrobial treatment in immunocompetent subjects. However, an inadequate immune response can lead to a prolonged and severe disease requiring antibiotics and more aggressive therapeutic approaches. OBJECTIVE: To comprehensively describe Campylobacter spp. infections in patients with common variable immunodeficiency (CVID). METHODS: A retrospective cohort of 14 CVID patients with Campylobacter infection and 95 CVID controls attending the immunology clinic at a large tertiary hospital was assessed. Immunological, clinical, and microbiological parameters were measured with median follow-up over 20 years in both cohorts. Patients were treated according to a novel algorithm for Campylobacter in antibody-deficient patients. RESULTS: Campylobacter patients had a higher proportion of CD21lowCD38low and transitional B cells (median 38.0% vs 14.2% and 5.4% vs 3.2%) and lower long-term average CD19+ B cells (median 0.06 vs 0.18 × 109/L) and CD4+ T cells (0.41 vs 0.62 × 109/L) in comparison with the controls. Similarly, Campylobacter patients showed a decline in B cells (median 0.02 vs 0.14 × 109/L), CD4+ T cells (0.33 vs 0.59 × 109/L), CD8+ T cells (0.26 vs 0.62 × 109/L), and natural killer cells (0.08 vs 0.18 × 109/L) over time. Antimicrobial resistance, especially to macrolides and fluoroquinolones, was common. Bacterial clearance with associated clinical improvement was obtained after a median of 20 and 113 days for acute Campylobacter (resolution within 3 mo of onset) and chronic Campylobacter (>3 mo) infections, respectively. Seven received first-line treatment (azithromycin or chloramphenicol), 4 second-line (neomycin), and 3 third-line (combination of tigecycline, chloramphenicol, and ertapenem; 1 received gentamicin owing to resistance to carbapenems). CONCLUSIONS: Our study highlights immunological and clinical characteristics of recurrent Campylobacter infections in patients with CVID. Our treatment algorithm was successful and should be evaluated in a larger cohort.

Treatment of inflammatory complications in common variable immunodeficiency (CVID): current concepts and future perspectives.

INTRODUCTION: Patients with common variable immunodeficiency (CVID) have a high frequency of inflammatory complications like autoimmune cytopenias, interstitial lung disease and enteropathy. These patients have poor prognosis and effective, timely, and safe treatment of inflammatory complications in CVID is essential, but guidelines and consensus on therapy are often lacking. AREAS COVERED: This review will focus on current medical treatment of inflammatory complications in CVID and point out some future perspectives based on literature indexed in PubMed. There are a number of good observational studies and case reports on treatment of specific complications, but randomized controlled trials are scarce. EXPERT OPINION: In clinical practice, the most urgent issues that need to be addressed are the preferred treatment of GLILD, enteropathy and liver disease. Treating the underlying immune dysregulation and immune exhaustion in CVID is an alternative approach that potentially could alleviate these and other organ-specific inflammatory complications. Therapies of potential interest and wider use in CVID include mTOR-inhibitors like sirolimus, JAK-inhibitors like tofacitinib, the monoclonal IL-12/23 antibody ustekinumab, the anti-BAFF antibody belimumab and abatacept. For all inflammatory complications, there is a need for prospective therapeutic trials, preferably randomized controlled trials, and multi-center collaborations with larger cohorts of patients will be essential.

Utilisation of immunoglobulin in New Zealand.

BACKGROUND: Immunoglobulin is an expensive and scarce resource and usage is increasing worldwide. Immunoglobulin is used to treat a variety of clinical conditions, particularly primary and acquired immunodeficiencies and immune-mediated neurological disorders. As immunoglobulin usage continues to increase, plasma collection must increase accordingly in order to sustain immunoglobulin production. The New Zealand Blood Service (NZBS) is the provider of immunoglobulin in New Zealand (NZ). Information regarding national immunoglobulin usage warrants analysis given the rise in usage. AIMS: To review immunoglobulin usage in NZ with a focus on the trend in the amount used, number of patients, clinical indications and compliance with international guidelines. A comparison with international immunoglobulin usage was performed. The impact on national plasma collection was reviewed. METHODS: Data on immunoglobulin usage, number of patients and plasma collection over the past decade were obtained from the NZBS Tableau database. Data from international literature were reviewed. RESULTS: Immunoglobulin usage in NZ has been increasing over the past decade, with an annual growth rate of 6.4%. The three main indications for immunoglobulin are primary immunodeficiency disorders, chronic inflammatory demyelinating polyneuropathy (CIDP) and acquired hypogammaglobulinaemia secondary to haematological malignancies. Prominent growth in usage is evident for CIDP and acquired hypogammaglobulinaemia. Immunoglobulin usage in NZ is low compared with other countries, such as Australia and the United States. There has been a marked increase in plasma donations in order to keep up with immunoglobulin demand. CONCLUSIONS: Immunoglobulin is a strategic resource and appropriate usage is critical to regulate demand.

Successful Treatment of Granulomatous-lymphocytic Interstitial Lung Disease in a Patient with CTLA-4 Deficiency.

Common variable immunodeficiency (CVID) causes granulomatous-lymphocytic interstitial lung disease (GLILD) and has a poor prognosis. We herein report a case of GLILD in a 49-year-old woman with CTLA-4 deficiency-associated CVID. The patient presented with dyspnea that had worsened over the past two years. A laboratory examination revealed hypoglobulinemia and pancytopenia. Chest computed tomography showed diffuse infiltrative and granular shadows in the bilateral interstitium. A flow cytometric analysis of blood cells and genetic testing confirmed CTLA-4 deficiency. We performed video-assisted thoracoscopic surgery for the pathological diagnosis of GLILD and to exclude infection and malignancy. Corticosteroid treatment successfully improved the condition of the patient.

Good Long-Term Outcome Following Liver Transplant in a Patient With Common Variable Immunodeficiency Syndrome Despite Multiple Infections and Recurrent Nodular Regenerative Hyperplasia.

Common variable immunodeficiency can be associated with various hepatic conditions, the most common being nodular regenerative hyperplasia. Multiple cases of liver transplant in adults with common variable immunodeficiency have been reported. Here, we report a 51-year-old man with common variable immunodeficiency and noncirrhotic portal hypertension due to nodular regenerative hyperplasia who underwent liver transplant. The patient received tacrolimus/steroid immunosuppression and remained rejection free; however, he developed cytomegalovirus infection, disseminated nocardiosis, Pseudomonas pneumonia, and Clostridioides difficile- associated colitis. All infections were successfully managed. The graft was well functioning after 18 months; however, alkaline phosphatase remained elevated and a liver biopsy showed evidence of recurrent nodular regenerative hyperplasia. The patient was started on a steroid taper, which led to normalization of the alkaline phosphatase. Two years later, a repeat biopsy confirmed recurrent nodular regenerative hyperplasia. Immunosuppression was kept low, and intravenous immunoglobulin infusions were continued. More than 10 years later, the patient is alive with a functioning graft. This case emphasizes that intensified prophylaxis for infections and less intense immunosuppression may be strategies to enable long-term survival in liver transplant recipients with common variable immunodeficiency and nodular regenerative hyperplasia relapse despite recently reported poor outcomes in this patient population.

The Uncomplicated Course of COVID-19 in Primary Immunodeficiency Patients: A Report of 14 Common Variable Immunodeficiency Patients.

Coronavirus disease 2019 (COVID-19) affects millions of people worldwide. Clinical manifestations range from asymptomatic to severe viral pneumonia. CVID patients with COVID-19 infection are not adequately studied. In some studies, CVID patients had higher mortality rates, although other studies showed that CVID patients might have an uncomplicated COVID-19 infection. We describe 14 cases of COVID-19 infection in Iranian CVID patients in this study, including clinical manifestations, laboratory findings, and treatment strategies. There were 29% of patients with mild disease, 43% with moderate disease, and 29% with severe disease in this study. A critical case and a death occurred in none of our patients. There were six cases of infection more than two weeks after receiving the second dose of Sinopharm BIBP COVID-19 vaccine; all had mild to moderate disease. Among these patients, Remdesivir was the most frequently prescribed medication. According to this study, most of our patients presented with an uncomplicated disease course.

Long Term Norovirus Infection in a Patient with Severe Common Variable Immunodeficiency.

Norovirus is the most common cause of acute non-bacterial gastroenteritis. Immunocompromised patients can become chronically infected, with or without symptoms. In Europe, common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity. A potentially severe complication is CVID-associated enteropathy, a disorder with similar histopathology to celiac disease. Studies suggest that chronic norovirus infection may be a contributor to CVID enteropathy, and that the antiviral drug ribavirin can be effective against norovirus. Here, a patient with CVID-like disease with combined B- and T-cell deficiency, had chronic norovirus infection and enteropathy. The patient was routinely administered subcutaneous and intravenous immunoglobulin replacement therapy (SCIg and IVIg). The patient was also administered ribavirin for ~7.5 months to clear the infection. Stool samples (collected 2013-2016) and archived paraffin embedded duodenal biopsies were screened for norovirus by qPCR, confirming a chronic infection. Norovirus genotyping was done in 25 stool samples. For evolutionary analysis, the capsid (VP1) and polymerase (RdRp) genes were sequenced in 10 and 12 stool samples, respectively, collected before, during, and after ribavirin treatment. Secretor phenotyping was done in saliva, and serum was analyzed for histo-blood group antigen (HBGA) blocking titers. The chronic norovirus strain formed a unique variant subcluster, with GII.4 Den Haag [P4] variant, circulating around 2009, as the most recent common ancestor. This corresponded to the documented debut of symptoms. The patient was a secretor and had HBGA blocking titers associated with protection in immunocompetent individuals. Several unique amino acid substitutions were detected in immunodominant epitopes of VP1. However, HBGA binding sites were conserved. Ribavirin failed in treating the infection and no clear association between ribavirin-levels and quantity of norovirus shedding was observed. In conclusion, long term infection with norovirus in a patient with severe CVID led to the evolution of a unique norovirus strain with amino acid substitutions in immunodominant epitopes, but conservation within HBGA binding pockets. Regularly administered SCIg, IVIg, and ~7.5-month ribavirin treatment failed to clear the infection.

[Antibody deficiencies in adults. Forty years of follow up]. / Inmunodeficiencias humorales en pacientes adultos. Cuatro décadas de seguimiento.

Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in primary (PAD) when there is an intrinsic immune defect, or secondary (SAD) to other diseases or drugs. The aim of our study was to review the evolutio n of AD assisted at the Immunology Unit, Hospital Durand between 1982 and 2020, divided into two periods: Period I (1982-2009) and Period II (2010-2020); to evaluate their growth, epidemiologic features and treatment options. A total of 205 patients were identified, 176 (85.8%) with PAD and 29 (14.2%) with SAD. The most frequent PAD were common variable immunodeficiency in 104 (59%) patients, X linked agammaglobulinemia in 17 (9.6%) and selective IgA deficiency in 26 (14.8%). Genetic defects were found in 25 (14.2%) patients with PAD. SAD cases were associated with rituximab in 21 (72.4%) subjects, haematological disease in three (10.2%) and with antiepileptic drugs in other three; 161 (78.5%) patients were treated with immunoglobulins, 140 (87%) PAD y 21 (13%) SAD; 152 (94.4%) received intravenous immunoglobulins and nine (5.6%) subcutaneous immunoglobulins. Thirty (19.7%) patients treated at first with intravenous immunoglobulins changed to subcutaneous formulations. The increase in number of patients between both periods was greater than 250%, and more than 700% in patients added per year. SAD growth was greater than twice times comparing with PAD. By the end of the study 125 patients continued in follow up, 80% PAD y 20% SAD and 14 died.

Las inmunodeficiencias humorales (IDH) comprenden un grupo de enfermedades caracterizadas por una deficiente respuesta mediada por anticuerpos. Se clasifican en primarias (IDHP), causadas por defectos propios del sistema inmune, o secundarias (IDHS) a otras enfermedades o fármacos. Nuestro objetivo fue revisar la evolución de las IDH asistidas en la Unidad Inmunología del Hospital Durand entre 1982 y 2020, dividido en dos periodos, Periodo I (1982-2009) y Periodo II (2010-2020); para evaluar el crecimiento de éstas, sus características epidemiológicas y las formas de tratamiento. Se evaluaron 205 pacientes, 176 (85.8%) IDHP y 29 (14.2%) IDHS. Las IDHP más diagnosticadas fueron: inmunodeficiencia común variable en 104 (59%) pacientes, agammaglobulinemia ligada al cromosoma X en 17 (9.6%) y deficiencia selectiva de IgA en 26 (14.8%). En 25 (14.2%) IDHP se realizó un diagnóstico molecular. Las causas de IDHS fueron: secundaria a rituximab en 21 (72.4%) pacientes, enfermedades hematológicas en tres (10.2%) y fármacos antiepilépticos en tres. Un total de 161 (78.5%) pacientes recibieron gammaglobulina, 140 (87%) IDHP y 21 (13%) IDHS; 152 (94.4%) fueron tratados con gammaglobulina endovenosa y nueve (5.6%) con gammaglobulina subcutánea. De los tratados inicialmente con forma endovenosa, 30 (19.7%) cambiaron a subcutánea. El crecimiento en la cantidad de pacientes entre ambos periodos del estudio fue mayor al 250%, y al 700% en pacientes incorporados por año. El crecimiento de las IDHS con relación al de las IDHP fue más del doble. Al finalizar el estudio 125 pacientes continuaban en seguimiento, 80% IDHP y 20% IDHS, y 14 fallecieron.

Ribavirin-resistant chronic norovirus infection-associated enteropathy in common variable immunodeficiency. Case report and review of the literature.

Chronic Norovirus infection is particularly challenging in patients with common variable immunodeficiency (CVID) because of their inability to achieve viral clearance and the risk of developing enteropathy leading to intestinal villous atrophy and malabsorption. To date, therapeutic options to eliminate the virus are limited and only ribavirin has been shown to induce viral clearance in norovirus enteropathy associated with CVID. We report a case of a 48-year-old female patient diagnosed with CVID enteropathy possibly related to norovirus infection who failed a ribavirin-based therapy despite dosage optimization through drug plasma level monitoring.

Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients.

Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14+ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.

Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency.

BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced. RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus-infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection. CONCLUSIONS: Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments.

Altered Plasma Fatty Acids Associate with Gut Microbial Composition in Common Variable Immunodeficiency.

PURPOSE: Fatty acid (FA) abnormalities are found in various inflammatory disorders and have been related to disturbed gut microbiota. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with altered gut microbial composition. We hypothesized that there is an altered FA profile in CVID patients, related to gut microbial dysbiosis. METHODS: Plasma FAs were measured in 39 CVID patients and 30 healthy controls. Gut microbial profile, a food frequency questionnaire, and the effect of the oral antibiotic rifaximin were investigated in CVID patients. RESULTS: The n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) (1.4 [1.0-1.8] vs. 1.9 [1.2-2.5], median (IQR), P < 0.05), and docosahexaenoic acid (DHA) (3.2 [2.4-3.9] vs. 3.5 [2.9-4.3], P < 0.05), all values expressed as weight percent of total plasma FAs, were reduced in CVID compared to controls. Also, n-6 PUFAs (34.3 ± 3.4 vs. 37.1 ± 2.8, mean ± SD, P < 0.001) and linoleic acid (LA) (24.5 ± 3.3 vs. 28.1 ± 2.7, P < 0.0001) and the FA anti-inflammatory index (98.9 [82.1-119.4] vs. 117.0 [88.7-153.1], median (IQR), P < 0.05) were reduced in CVID. The microbial alpha diversity was positively associated with plasma n-6 PUFAs (r = 0.41, P < 0.001) and LA (r = 0.51, P < 0.001), but not n-3 PUFAs (P = 0.78). Moreover, a 2-week course of rifaximin significantly reduced the proportion of n-6 PUFAs (P = 0.04, UNIANOVA). Serum immunoglobulin G (IgG) levels correlated with plasma n-3 PUFAs (rho = 0.36, P = 0.03) and DHA (rho = 0.41, P = 0.009). CONCLUSION: We found a potentially unfavorable FA profile in CVID, related to low IgG levels. High plasma n-6 PUFAs were related to increased gut microbial diversity and altered by rifaximin therapy.