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The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital.

ABSTRACT:

Background

Common variable immunodeficiency disorders (CVIDs) represents a heterogeneous disease spectrum that includes recurrent infections and complications such as autoimmunity, inflammatory organ disease and an increased risk of cancer. A diagnostic delay is common in CVIDs patients.

Purpose

To determine the spectrum of clinical manifestations, immunological characteristics, and the time to diagnosis of 61 adult CVIDs and 18 patients with a partial antibody deficiency (SADNI and IgG subclass deficiency).

Methods

A retrospective cohort study was performed in patients who met the ESID/PAGID for CVIDs, IgG subclass deficiency and SADNI. Medical records were reviewed to obtain patient demographics, clinical and laboratory data.

Results

Infections were the main presentation of all antibody deficient patients and the number of patients with infections declined during IgG therapy. The development of bronchiectasis continued despite IgG therapy, as well as the development of autoinflammatory conditions. Non-infectious disease complications were present in 30% of CVIDs patients at the time of diagnosis and this increased to 51% during follow up despite IgG therapy. The most common complications were autoimmunity or lymphoproliferative disease. The median time to diagnosis was 10 years and in the patients with non-infectious complications the time to diagnosis was considerably longer when compared to the group of patients without complications (17.6 vs. 10.2 years, p?=?0.026).

Conclusion

In contrast to the partial antibody deficiencies we found a considerable delay in the diagnosis of CVIDs, especially in those patients who were dominated by non-infectious complications, and thus increased awareness would be beneficial. Pulmonary and other complications may continue despite adequate IgG replacement therapy suggesting other causes responsible for these complications.

SUBMITTER: Maarschalk-Ellerbroek LJ

PROVIDER: S-EPMC3443482 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital.

Maarschalk-Ellerbroek L J LJ Hoepelman A I M AI van Montfrans J M JM Ellerbroek P M PM

Journal of clinical immunology 20120413 5

<h4>Background</h4>Common variable immunodeficiency disorders (CVIDs) represents a heterogeneous disease spectrum that includes recurrent infections and complications such as autoimmunity, inflammatory organ disease and an increased risk of cancer. A diagnostic delay is common in CVIDs patients.<h4>Purpose</h4>To determine the spectrum of clinical manifestations, immunological characteristics, and the time to diagnosis of 61 adult CVIDs and 18 patients with a partial antibody deficiency (SADNI a ...[more]

PMID: 22526591

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Project description:BackgroundCommon variable immunodeficiency (CVID) is one of the most common primary immunodeficiency syndromes, affecting one in 25,000-50,000 people. Renal insufficiency occurs in approximately 2% of patients with CVID. To date, there are no case series of renal biopsies from patients with CVID, making it difficult to determine whether individual cases of renal disease in CVID represent sporadic events or are related to the underlying pathophysiology. We performed a retrospective analysis of renal biopsy specimens in our database from patients with a clinical history of CVID (n=22 patients, 27 biopsies).MethodsLight, immunofluorescence, and electron microscopy were reviewed. IgG subclasses, PLA2R immunohistochemistry, and THSD7A, EXT1, and NELL1 immunofluorescence were performed on all membranous glomerulopathy cases. CD3, CD4, CD8, and CD20 immunohistochemistry was performed on cases of tubulointerstitial nephritis.ResultsAKI and proteinuria were the leading indications for renal biopsy in patients with CVID. Immune-complex glomerulopathy was present in 12 of 22 (54.5%) cases, including nine cases with membranous glomerulopathy, one case with a C3 glomerulopathy, and one case with membranoproliferative GN with IgG3κ deposits. All membranous glomerulopathy cases were PLA2R, THSD7A, EXT1, and NELL1 negative. The second most common renal biopsy diagnosis was chronic tubulointerstitial nephritis, affecting 33% of patients. All tubulointerstitial nephritis cases showed tubulitis and a lymphocytic infiltrate with >90% CD3+ T cells. Other renal biopsy diagnoses within our cohort included acute tubular injury (n=1), amyloid light-chain amyloidosis (n=1), diabetic glomerulosclerosis (n=1), thin basement membranes (n=1), pauci-immune GN (n=1), and arterionephrosclerosis (n=1).ConclusionsMembranous glomerulopathy and tubulointerstitial nephritis were the predominant pathologic findings in patients with CVID. Membranous glomerulopathy cases in patients with CVID were IgG1 subclass dominant and showed mesangial immune deposits. Four of the membranous glomerulopathy cases had associated proliferation, with mesangial and/or endocapillary hypercellularity, with or without crescent formation. CVID should be considered as a potential cause when membranous glomerulopathy or chronic tubulointerstitial nephritis is seen in a young patient with a history of recurrent infections.

Project description:BackgroundCommon variable immunodeficiency disorders (CVID) are a group of rare innate disorders characterized by specific antibody deficiency and increased rates of infections, comorbidities and mortality. The burden of CVID in Europe has not been previously estimated. We performed a retrospective analysis of the European Society for Immunodeficiencies (ESID) registry data on the subset of patients classified by their immunologist as CVID and treated between 2004 and 2014. The registered deaths and comorbidities were used to calculate the annual average age-standardized rates of Years of Life Lost to premature death (YLL), Years Lost to Disability (YLD) and Disability Adjusted Life Years (DALY=YLL?+?YLD). These outcomes were expressed as a rate per 105 of the CVID cohort (the individual disease burden), and of the general population (the societal disease burden).ResultsData of 2700 patients from 23 countries were analysed. Annual comorbidity rates: bronchiectasis, 21.9%; autoimmunity, 23.2%; digestive disorders, 15.6%; solid cancers, 5.5%; lymphoma, 3.8%, exceeded the prevalence in the general population by a factor of 34.0, 7.6, 8.1, 2.4 and 32.6, respectively. The comorbidities of CVID caused 8722 (6069; 12,363) YLD/105 in this cohort, whereas 44% of disability burden was attributable to infections and bronchiectasis. The total individual burden of CVID was 36,785 (33,078, 41,380) DALY/105. With estimated CVID prevalence of ~?1/ 25,000, the societal burden of CVID ensued 1.5 (1.3, 1.7) DALY/105 of the general population. In exploratory analysis, increased mortality was associated with solid tumor, HR (95% CI): 2.69 (1.10; 6.57) p?=?0.030, lymphoma: 5.48 (2.36; 12.71) p?<?.0001 and granulomatous-lymphocytic interstitial lung disease: 4.85 (1.63; 14.39) p?=?0.005. Diagnostic delay (median: 4 years) was associated with a higher risk of death: 1.04 (1.02; 1.06) p?=?.0003, bronchiectasis: 1.03 (1.01; 1.04) p?=?.0001, solid tumor: 1.08 (1.04; 1.11) p?<?.0001 and enteropathy: 1.02 (1.00; 1.05) p?=?.0447 and stayed unchanged over four decades (p?=?.228).ConclusionsWhile the societal burden of CVID may seem moderate, it is severe to the individual patient. Delay in CVID diagnosis may constitute a modifiable risk factor of serious comorbidities and death but showed no improvement. Tools supporting timely CVID diagnosis should be developed with high priority.

Dataset Information

The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital.

Background

Purpose

Methods

Results

Conclusion

Publications

The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital.

Similar Datasets

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