X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses.</p> <p>Methods</p> <p>The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed.</p> <p>Results</p> <p>2 patients previously diagnosed with CVID associated with virtual absence of CD19⁺B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. <b>Patient 1</b>, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). <b>Patient 2</b>, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA</p> <p>Conclusion</p> <p>These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19⁺B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.</p

Climate, people and faunal succession on Java, Indonesia: evidence from Song Gupuh

Song Gupuh, a partially collapsed cave in the Gunung Sewu Limestones of East Java, Indonesia, contains over 16 m of deposits with a faunal sequence spanning some 70 ka. Major changes in the range of animals represented show the impact of climate change and humans. The Terminal Pleistocene and Early Holocene was a period of maximum biodiversity. Human use of Song Gupuh and other cave sites in the region also intensified significantly from ca. 12 ka, together with a new focus on exploitation of small-bodied species (macaque monkeys and molluscs), the first evidence for import of resources from the coast, and use of bone and shell tools. Human activity, especially after the onset of the Neolithic around 2.6 ka, subsequently contributed to a progressive loss of many species from the area, including tapir, elephant, Malayan bear, rhino and tiger, and this extinction process is continuing. We conclude by discussing the biogeographical significance of Song Gupuh in the context of other sites in Java (e.g. Punung, Wajak) and further afield (e.g. Liang Bua)

The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review

Primary immune deficiency disorders (PIDs) are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, prenatal diagnosis and is useful in defining new diseases. In this review we outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. It is written from the perspective of a laboratory offering a wide range of tests for a small developed country

Neurocranium versus Face: A Morphometric Approach with Classical Anthropometric Variables for Characterizing Patterns of Cranial Integration in Extant Hominoids and Extinct Hominins

The relative importance of the two main cranial complexes, the neurocranium and the splanchnocranium, has been examined in the five species of extant hominoids and in a huge sample of extinct hominins using six standard craniometric variables that measure the length, width and height of each cranial module. Factor analysis and two-block partial least squares were used for establishing the major patterns of developmental and evolutionary integration between both cranial modules. The results obtained show that all extant hominoids (including the anatomically modern humans) share a conserved pattern of developmental integration, a result that agrees with previous studies. The pattern of evolutionary integration between both cranial modules in australopiths runs in parallel to developmental integration. In contrast, the pattern of evolutionary and developmental integration of the species of the genus Homo is the opposite, which is probably the consequence of distinctive selective regimes for both hominin groups.JAPC, JMJA and PP received fundings from Ministerio de Ciencia e Innovación, Gobierno de España (http://www.idi.mineco.gob.es), project CGL2011-30334, and Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, España (http://www.juntadeandalucia.es/organismo​s/economiainnovacioncienciayempleo.html), project P11-HUM-7248 and Research Groups RNM-146 and HUM-607

Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed

Two interpretations of human evolution: Essentialism and Darwinism

Despite intensive studies of a large number of fossils discovered during the 20th century there is no consensus as to the interpretation of the process of hominin evolution. Some authors see as many as six genera and some 17 species, while others argue for a single lineage from Plio/Pleistocene until today. Such diversity of interpretations of the same facts indicates lack of a uniform theoretical basis underlying studies of human evolution. Debates can be resolved using basic principles of scientific inquiry - parsimony and falsification of null hypotheses. Hypothesis testing is now possible with respect to the evolution of basic hominin characteristics such as brain size, body size and the size of the dentition that have sample sizes of a few hundred individual data points each. These characters display a continuous change with time. Analyses of variance do not falsify the null hypothesis of the existence of only one species at any time - variances around regression lines on time do not differ from the variance observed in the single species of Homo sapiens - distributions of residuals are normal. Thus, splitting of the hominin lineage into coeval species can only be based on descriptive characteristics that are liable to errors of subjective judgment.Maciej Henneber

Phenotypic variability: Clinical presentation between the 6th year and the 60th year in a family with X-linked agammaglobulinemia

Karen Morwood, Helen Bourne, Ross Philpot, Michael Gold, David Gillis and Elizabeth M. Benso

Preface: research at Liang Bua, Flores, Indonesia

Excavations at Liang Bua, Flores, Indonesia, have yielded evidence for an endemic human species, Homo floresiensis, a population that occupied the cave between w95–17 ka. This discovery has major implications for early hominin evolution and dispersal in Africa and Asia, attracting worldwide interest. This preface describes the rationale for the excavations in historical, geographical, and wider research contexts, as well as the methods used. It also introduces the other papers on aspects of Liang Bua research that feature in this edition of the Journal of Human Evolution

Preface: research at Liang Bua, Flores, Indonesia

Excavations at Liang Bua, Flores, Indonesia, have yielded evidence for an endemic human species, 'Homo floresiensis', a population that occupied the cave between ~95-17 ka. This discovery has major implications for early hominin evolution and dispersal in Africa and Asia, attracting worldwide interest. This preface describes the rationale for the excavations in historical, geographical, and wider research contexts, as well as the methods used. It also introduces the other papers on aspects of Liang Bua research that feature in this edition of the 'Journal of Human Evolution'