Long-term study of a female hyper-IgM immunodeficiency

Hyper-IgM immunodeficiency (HIM) is an immunological disorder characterized by normal or elevated serum IgM levels, and reduced serum IgG and IgA levels, due to the disruption of immunoglobulin class switching in B cells. X-linked hyper-IgM is caused by the defective expression of the CD40 ligand on activated T cells, which induces immunoglobulin class switching along with some cytokines, such as interleukin 4, by the signal transduction of CD40 in B cells. We report on a Japanese girl who initially showed low serum IgM, IgG and IgA levels like patients with common variable immunodeficiency; however, in the course of time, serum IgG levels became reduced and serum IgM levels increased, resulting in the typical immunoglobulin profile of HIM. Neutropenia, one of the features of X-linked HIM, was not observed. In spite of extremely low serum IgG levels, she did not show any predisposition to severe infection, even without gammaglobulin replacement therapy. No mutation of the CD40 ligand or CD40 was detected. Sequencing of the complementarity-determining region of immunoglobulin heavy-chain genes in peripheral B lymphocytes revealed that they were all in frame, and insertion of the N region was detected. These results indicate that the heavy-chain gene rearrangement in the patient's B cells is intact. Non-X-linked HIM has heterogeneous pathogenetic mechanisms, and some groups may show the resistance to infection at the healthy donor level. The underlying defects in non-X-linked HIM might be specifically involved in class switching.     

Immunologic studies of three family members with the immunodeficiency with hyper-IgM syndrome

We report the results of immunologic studies in a family in which the father (III-5) and his two daughters (IV-7 and IV-8) had the hyper-IgM syndrome (IHIS). Repeated immunoglobulin levels done on III-5 showed a typical IHIS pattern: low IgG, traces of IgA, and high IgM. IV-7, who also had stage IIA Hodgkin's disease, had a similar pattern except after irradiation therapy to sites of disease, when IgM dropped to normal range while IgG and IgA remained low. IV-8, on the other hand, had normal IgG and IgA and moderately elevated IgM until age 18 months, when she gradually developed the IHIS pattern. All three patients had normal numbers of B cells (sIg) and of T cells, although IV-7 had increased suppression. Finally, all three patients shared the A3,B7 haplotype and none was blood type O. IHIS is not necessarily X linked, is not associated with blood type O, and appears to be heterogeneous even within the same family. Inheritance in this family is apparently autosomal dominant and the father may represent a new mutation.     

A sporadic case of apparent Crouzon''s syndrome with extracraniofacial manifestations

A case is presented which may represent a fresh mutation with craniofacial characteristics of Crouzon's syndrome and skeletal abnormalities suggestive of Carpenter's syndrome together with mild skin syndactyly.     

Ocular manifestations of acquired immunodeficiency syndrome in Korea

The clinical features of HIV/AIDS-related ocular manifestations in Korean patients were investigated in this study. Data on 200 consecutive Korean patients diagnosed with AIDS who visited the Seoul National University Hospital from January 2003 to June 2008 were reviewed. Fifty-seven patients (28.5%) had ocular manifestations, and they showed significantly lower CD4+ T cell count than patients without ocular manifestations. Among them, 23 (40.3%) patients showed retinal microvasculopathy, and 22 (38.5%) patients showed cytomegalovirus (CMV) retinitis. Other manifestations included retinal vein occlusion (n = 4), herpes zoster ophthalmicus (n = 4), syphilitic uveitis (n = 2), acute retinal necrosis (n = 1), and progressive outer retinal necrosis (n = 1). The mean CD4+ lymphocyte counts of the patients with retinal microvasculopathy and cytomegalovirus retinitis were 108.5 cells/μL and 69.4 cells/μL, respectively. In conclusion, ocular manifestations including CMV retinitis are common complications in Korean patients with AIDS even in the era of highly active anti-retroviral therapy. Compared to previous reports in western countries, prevalence of CMV retinitis is relatively low and CD4+ lymphocytes count at the time of diagnosis is relatively high.     

A case of Kabuki (Niikawa-Kuroki) syndrome associated with manifestations resembling C-trigonocephaly syndrome

We report a 2-year-old boy with overlapping manifestations of the Kabuki (Niikawa-Kuroki) and Opitz trigonocephaly syndromes. The proband was initially diagnosed with Opitz trigonocephaly syndrome on the basis of metopic craniosynostosis, upslanting palpebral fissures, high arched palate, redundant skin folds at the back of the neck, ventricular septal defect, broad flat thumbs, bilateral single palmar creases, left talipes equinovarus, eventration of right hemidiaphragm, and bilateral inguinal hernia. However, as he grew older, his facial profile changed to that typical of Kabuki syndrome.     

A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency

We present a boy with hyper-IgM syndrome with a previously not reported mutation in the CD40 ligand gene. He also had a concomitant natural killer (NK) cell deficiency. He had no CD56⁺ or CD16⁺ cells and no NK activity as determined in 4 h chromium release cytotoxicity assay. After 5 days in culture with IL-2-containing medium, however, his peripheral blood mononuclear cells lysed both NK-sensitive and NK-resistant targets, showing that he had lymphokine-activated killer cell precursors in the circulation. Due to the associated neutropenia, he was treated with granulocyte colony-stimulating factor (G-CSF) and responded well. In the same period we observed a transient increase in the number of NK cells. Isolated NK cell deficiencies are extremely rare. We suggest that the defect in our patient is part of the hyper-IgM syndrome, probably representing the phenotype of the new mutation described. Thus, it is possible that both the neutropenia and the NK cell deficiency are due to lack of growth-promoting signals normally delivered by the CD40 ligand.     

HCV infection in a patient with hyper-IgM syndrome

The association between an acquired form of hyper-IgM syndrome and a chronic hepatitis C virus (HCV) infection in a 71-year-old female patient is described. Both diseases were diagnosed at the age of 58 years. She was started on intramuscular and then intravenous immunoglobulin replacement therapy. HCV RNA was detected in 1992. The patient remained in well-balanced clinical condition until 1994, when total and specific anti-HCV IgM levels increased and the patient developed an IgM monoclonal gammopathy. Adherent cells and B cells were HCV RNA positive, while T cells were HCV RNA negative. Anti-IgM reactivity was specifically directed to the core antigen of the HCV. The patient we describe showed a picture of a late-onset form of hypogammaglobulinemia with a progressive increase in IgM antibodies, possibly due to the concomitant HCV infection. It is possible that the immunodeficiency might also result from the HCV infection, with formation of specific antibodies belonging to the IgM class, and that the worsening of the clinical condition may be directly related to the persistent viral infection.     

A case of common variable immunodeficiency syndrome associated with Takayasu arteritis.

BACKGROUND: Association of common variable immunodeficiency (CVID) with Takayasu arteritis has rarely been reported. OBJECTIVE: To describe a case of Takayasu arteritis in a 53-year-old Hispanic woman with CVID undergoing long-term (3-year) intravenous immunoglobulin (IVIG) treatment. METHODS: The patient's serum immunoglobulin levels and antibody titers to measles, mumps, and rubella were measured. She also underwent angiography of the large vessels. RESULTS: Low to undetectable serum IgA, IgM, and IgG levels and low antibody titers to mumps, measles, and rubella were consistent with the diagnosis of CVID. The angiogram showed narrowing of the proximal left subclavian artery (2-3 mm in diameter). CONCLUSIONS: This patient developed Takayasu arteritis while receiving IVIG for CVID. She clinically improved after her IVIG dose was increased. To our knowledge, this is the second reported case of Takayasu arteritis associated with CVID.     

A case of vasculitis syndrome associated with epididymitis]

A case of vasculitis syndrome associated with epididymitis is reported. A 56-year-old male presented with the sudden left testicular pain and fever. He came to the department of urology in our hospital, and was treated with antibiotics and anti-tuberculous drugs. However, the testicular pain was not relieved as well as the fever. In January 5, 1993, he was admitted. He had lost 6 kg. Physical examination revealed pyrexia and blood pressure of 150/91 mmHg. Laboratory finding revealed leukocytosis, thrombocytosis, and erythrocyte sedimentation rate of 100 mm/hr. On serological examination, the C-reactive protein was positive. We suspected this case as a polyarteritis nodosa, then he was given prednisolone. On January 20, 1993, left orchidectomy and spermatic cord biopsy was performed and non-necrotizing vasculitis was found. On August 10, cyclophoaphamide was added and his symptom disappeared. Although polyarteritis nodosa is well known as the vasculitis affecting the epididymis, it was rare that initial manifestation was testicular pain. In this case necrotizing vasculitis was not proven, but we diagnosed this case as a vasculitis in which the initial symptom was the epididymitis.     

Expansion of the phenotype in Hennekam syndrome: A case with new manifestations

We report on a female with lymphedema, facial anomalies, intestinal lymphangiectasia, and moderate mental retardation consistent with the diagnosis of Hennekam syndrome. In addition, she had a number of other anomalies not previously described in this autosomal recessive disorder, including a congenital heart defect, atretic ear canals, vesicoureteral reflux, and rectal prolapse. Am. J. Med. Genet. 71:211–214, 1997. © 1997 Wiley-Liss, Inc.     

Wrinkly skin syndrome: phenotype and additional manifestations

The wrinkly skin syndrome is an autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, multiple musculoskeletal abnormalities, microcephaly, and mental retardation. Our patient is characteristic of the syndrome as previously described, and confirms the presence of mental retardation and microcephaly as component manifestations, with the additional findings of connective tissue abnormalities evidenced by an atrial septal aneurysm.     

Histoplasmosis in patients with acquired immunodeficiency syndrome. Hematologic and bone marrow manifestations

In areas where Histoplasma capsulatum infections are endemic in the United States, there is an increasing frequency of progressive disseminated histoplasmosis (PDH) as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). The bone marrow and peripheral blood (PB) specimens in 13 patients with AIDS and PDH were reviewed. Anemia, leukopenia, and thrombocytopenia were found in 12, 10, and 7 patients, respectively. Circulating organisms were detected in the blood smears or buffy coat preparations from five patients and were associated with PB nRBCs and severe absolute monocytopenia. Morphologically, the marrow specimens showed one of four patterns: (1) no morphologic evidence of infection (two patients, one with a positive marrow culture); (2) discrete granulomas (two patients, both with positive marrow cultures); (3) lymphohistiocytic aggregates (six patients, four with positive marrow cultures); and (4) diffuse macrophage infiltrates (three patients, all with positive marrow cultures). Morphologic examination of the bone marrow combined with cultures is useful in diagnosing disseminated histoplasmosis in patients with AIDS. However, the morphologic findings in the bone marrow may be different in patients with AIDS compared with non-AIDS patients, and seemingly nondiagnostic morphologic features must be approached with a high degree of suspicion in diagnosing infections with H. capsulatum in this population.     

Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.